3496 (G > A)

General info

Mitimpact ID
MI.11153
Chr
chrM
Start
3496
Ref
G
Alt
A
Gene symbol
MT-ND1 Extended gene annotation
Gene position
190
Gene start
3307
Gene end
4262
Gene strand
+
Codon substitution
GCC/ACC
AA pos
64
AA ref
A
AA alt
T
Functional effect
missense
OMIM ID
HGVS
NC_012920.1:g.3496G>A
HGNC ID
RC complex
I
Ensembl gene ID
Ensembl protein ID
Ensembl transcript ID
Uniprot ID
Uniprot name
Ncbi gene ID
Ncbi protein ID
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Conservation

PhyloP 100v
-2.57 Conservation Score
PhyloP 470way
0.458 Conservation Score
PhastCons 100v
0 Conservation Score
PhastCons 470way
0.043 Conservation Score

Pathogenicity predictors

PolyPhen2
Benign Score and details of the predictor
SIFT
Neutral Score and details of the predictor
SIFT4G
Tolerated Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Neutral Score and details of the predictor
SNPDryad
Neutral Score and details of the predictor
MutationTaster
Polymorphism Score and details of the predictor
fathmm
Tolerated Score and details of the predictor
AlphaMissense
Likely benign Score and details of the predictor
CADD
Neutral Score and details of the predictor
PROVEAN
Tolerated Score and details of the predictor
Mutation Assessor
Neutral Score and details of the predictor
EFIN SP
Neutral Score and details of the predictor
EFIN HD
Neutral Score and details of the predictor
MLC
Neutral Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Neutral Score and details of the meta-predictor
APOGEE2
Benign Score and details of the meta-predictor
CAROL
Neutral Score and details of the meta-predictor
Condel
Deleterious Score and details of the meta-predictor
COVEC WMV
Neutral Score and details of the meta-predictor
MtoolBox
Neutral Score and details of the meta-predictor
DEOGEN2
Tolerated Score and details of the meta-predictor
Meta SNP
.

Cancer-specific predictors

PolyPhen2 transf
High impact Score and details of the cancer-specific predictor
SIFT transf
Medium impact Score and details of the cancer-specific predictor
MutationAssessor transf
Low impact Score and details of the cancer-specific predictor
CHASM
Neutral Score and details of the cancer-specific predictor

Databases of Frequencies and Phenotypes

Clinvar ID
Clinvar ALLELEID
680895
Clinvar CLNDISDB
Mondo:mondo:0009723, medgen:c0023264, omim:256000, orphanet:506
Clinvar CLNDN
Leigh syndrome
Clinvar CLNSIG
Uncertain significance
MITOMAP Allele
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease Hom/Het
./.
MITOMAP General GenBank Freq
0.0131%
MITOMAP General GenBank Seqs
8
MITOMAP General GenBank Curated refs
MITOMAP Variant Class
polymorphism
Gnomad AN
56428
Gnomad AC hom
3
Gnomad AF hom
5.31e-05
Gnomad AC het
1
Gnomad AF het
1.77e-05
Gnomad filter
Pass
HelixMTdb AC hom
6
HelixMTdb AF hom
3.06e-05
HelixMTdb AC het
1
HelixMTdb AF het
5.1e-06
HelixMTdb mean ARF
0.86726
HelixMTdb max ARF
0.86726
ToMMo JPN54K AC
.
ToMMo JPN54K AF
.
ToMMo JPN54K AN
.
COSMIC 90
COSM5653110
dbSNP 156

Residue interaction

EVmutation
Site A-B InterP
Site A-B IntraP
ΔΔG intra
ΔΔG intra interface
ΔΔG inter

Compensated Pathogenic Deviations

Frequency
.
AA ref
.
CPD AA alt
.
Aln pos
.
RefSeq protein ID
.
Species name
.
Ncbi taxon ID
.

3496 (G > C)

General info

Mitimpact ID
MI.11155
Chr
chrM
Start
3496
Ref
G
Alt
C
Gene symbol
MT-ND1 Extended gene annotation
Gene position
190
Gene start
3307
Gene end
4262
Gene strand
+
Codon substitution
GCC/CCC
AA pos
64
AA ref
A
AA alt
P
Functional effect
missense
OMIM ID
HGVS
NC_012920.1:g.3496G>C
HGNC ID
RC complex
I
Ensembl gene ID
Ensembl protein ID
Ensembl transcript ID
Uniprot ID
Uniprot name
Ncbi gene ID
Ncbi protein ID
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Conservation

PhyloP 100v
-2.57 Conservation Score
PhyloP 470way
0.458 Conservation Score
PhastCons 100v
0 Conservation Score
PhastCons 470way
0.043 Conservation Score

Pathogenicity predictors

PolyPhen2
Benign Score and details of the predictor
SIFT
Neutral Score and details of the predictor
SIFT4G
Tolerated Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Neutral Score and details of the predictor
SNPDryad
Neutral Score and details of the predictor
MutationTaster
Polymorphism Score and details of the predictor
fathmm
Tolerated Score and details of the predictor
AlphaMissense
Ambiguous Score and details of the predictor
CADD
Neutral Score and details of the predictor
PROVEAN
Tolerated Score and details of the predictor
Mutation Assessor
Neutral Score and details of the predictor
EFIN SP
Neutral Score and details of the predictor
EFIN HD
Neutral Score and details of the predictor
MLC
Neutral Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Neutral Score and details of the meta-predictor
APOGEE2
Vus Score and details of the meta-predictor
CAROL
Neutral Score and details of the meta-predictor
Condel
Deleterious Score and details of the meta-predictor
COVEC WMV
Neutral Score and details of the meta-predictor
MtoolBox
Neutral Score and details of the meta-predictor
DEOGEN2
Tolerated Score and details of the meta-predictor
Meta SNP
.

Cancer-specific predictors

PolyPhen2 transf
Medium impact Score and details of the cancer-specific predictor
SIFT transf
Medium impact Score and details of the cancer-specific predictor
MutationAssessor transf
Medium impact Score and details of the cancer-specific predictor
CHASM
Neutral Score and details of the cancer-specific predictor

Databases of Frequencies and Phenotypes

Clinvar ID
.
Clinvar ALLELEID
.
Clinvar CLNDISDB
.
Clinvar CLNDN
.
Clinvar CLNSIG
.
MITOMAP Allele
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease Hom/Het
./.
MITOMAP General GenBank Freq
.
MITOMAP General GenBank Seqs
.
MITOMAP General GenBank Curated refs
.
MITOMAP Variant Class
.
Gnomad AN
56431
Gnomad AC hom
0
Gnomad AF hom
0.0
Gnomad AC het
0
Gnomad AF het
0.0
Gnomad filter
Npg
HelixMTdb AC hom
0
HelixMTdb AF hom
0.0
HelixMTdb AC het
.
HelixMTdb AF het
0.0
HelixMTdb mean ARF
0.0
HelixMTdb max ARF
.
ToMMo JPN54K AC
.
ToMMo JPN54K AF
.
ToMMo JPN54K AN
.
COSMIC 90
.
dbSNP 156

Residue interaction

EVmutation
Site A-B InterP
Site A-B IntraP
ΔΔG intra
ΔΔG intra interface
ΔΔG inter

Compensated Pathogenic Deviations

Frequency
.
AA ref
.
CPD AA alt
.
Aln pos
.
RefSeq protein ID
.
Species name
.
Ncbi taxon ID
.

General info

Mitimpact ID
MI.11154
Chr
chrM
Start
3496
Ref
G
Alt
T
Gene symbol
MT-ND1 Extended gene annotation
Gene position
190
Gene start
3307
Gene end
4262
Gene strand
+
Codon substitution
GCC/TCC
AA pos
64
AA ref
A
AA alt
S
Functional effect
missense
OMIM ID
HGVS
NC_012920.1:g.3496G>T
HGNC ID
RC complex
I
Ensembl gene ID
Ensembl protein ID
Ensembl transcript ID
Uniprot ID
Uniprot name
Ncbi gene ID
Ncbi protein ID
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
-2.57 Conservation Score
PhyloP 470way
0.458 Conservation Score
PhastCons 100v
0 Conservation Score
PhastCons 470way
0.043 Conservation Score

Pathogenicity predictors

PolyPhen2
Benign Score and details of the predictor
SIFT
Neutral Score and details of the predictor
SIFT4G
Tolerated Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Neutral Score and details of the predictor
SNPDryad
Neutral Score and details of the predictor
MutationTaster
Polymorphism Score and details of the predictor
fathmm
Tolerated Score and details of the predictor
AlphaMissense
Likely benign Score and details of the predictor
CADD
Neutral Score and details of the predictor
PROVEAN
Tolerated Score and details of the predictor
Mutation Assessor
Neutral Score and details of the predictor
EFIN SP
Neutral Score and details of the predictor
EFIN HD
Neutral Score and details of the predictor
MLC
Neutral Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Neutral Score and details of the meta-predictor
APOGEE2
Benign Score and details of the meta-predictor
CAROL
Neutral Score and details of the meta-predictor
Condel
Deleterious Score and details of the meta-predictor
COVEC WMV
Neutral Score and details of the meta-predictor
MtoolBox
Neutral Score and details of the meta-predictor
DEOGEN2
Tolerated Score and details of the meta-predictor
Meta SNP
.

Cancer-specific predictors

PolyPhen2 transf
High impact Score and details of the cancer-specific predictor
SIFT transf
Medium impact Score and details of the cancer-specific predictor
MutationAssessor transf
Low impact Score and details of the cancer-specific predictor
CHASM
Neutral Score and details of the cancer-specific predictor

Databases of Frequencies and Phenotypes

Clinvar ID
.
Clinvar ALLELEID
.
Clinvar CLNDISDB
.
Clinvar CLNDN
.
Clinvar CLNSIG
.
MITOMAP Allele
MITOMAP Disease Clinical info
Lhon
MITOMAP Disease Status
Reported / secondary
MITOMAP Disease Hom/Het
+/-
MITOMAP General GenBank Freq
0.018%
MITOMAP General GenBank Seqs
11
MITOMAP General GenBank Curated refs
MITOMAP Variant Class
polymorphism;disease
Gnomad AN
56429
Gnomad AC hom
0
Gnomad AF hom
0.0
Gnomad AC het
0
Gnomad AF het
0.0
Gnomad filter
Npg
HelixMTdb AC hom
16
HelixMTdb AF hom
8.16e-05
HelixMTdb AC het
0
HelixMTdb AF het
0.0
HelixMTdb mean ARF
0.0
HelixMTdb max ARF
.
ToMMo JPN54K AC
610
ToMMo JPN54K AF
0.011233
ToMMo JPN54K AN
54302
COSMIC 90
.
dbSNP 156

Residue interaction

EVmutation
Site A-B InterP
Site A-B IntraP
ΔΔG intra
ΔΔG intra interface
ΔΔG inter

Compensated Pathogenic Deviations

Frequency
.
AA ref
.
CPD AA alt
.
Aln pos
.
RefSeq protein ID
.
Species name
.
Ncbi taxon ID
.
~ 3496 (G/A) 3496 (G/C) 3496 (G/T)
~ 3496 (GCC/ACC) 3496 (GCC/CCC) 3496 (GCC/TCC)
MitImpact id MI.11153 MI.11155 MI.11154
Chr chrM chrM chrM
Start 3496 3496 3496
Ref G G G
Alt A C T
Gene symbol MT-ND1 MT-ND1 MT-ND1
Extended annotation mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1
Gene position 190 190 190
Gene start 3307 3307 3307
Gene end 4262 4262 4262
Gene strand + + +
Codon substitution GCC/ACC GCC/CCC GCC/TCC
AA position 64 64 64
AA ref A A A
AA alt T P S
Functional effect general missense missense missense
Functional effect detailed missense missense missense
OMIM id 516000 516000 516000
HGVS NC_012920.1:g.3496G>A NC_012920.1:g.3496G>C NC_012920.1:g.3496G>T
HGNC id 7455 7455 7455
Respiratory Chain complex I I I
Ensembl gene id ENSG00000198888 ENSG00000198888 ENSG00000198888
Ensembl transcript id ENST00000361390 ENST00000361390 ENST00000361390
Ensembl protein id ENSP00000354687 ENSP00000354687 ENSP00000354687
Uniprot id P03886 P03886 P03886
Uniprot name NU1M_HUMAN NU1M_HUMAN NU1M_HUMAN
Ncbi gene id 4535 4535 4535
Ncbi protein id YP_003024026.1 YP_003024026.1 YP_003024026.1
PhyloP 100V -2.57 -2.57 -2.57
PhyloP 470Way 0.458 0.458 0.458
PhastCons 100V 0 0 0
PhastCons 470Way 0.043 0.043 0.043
PolyPhen2 benign benign benign
PolyPhen2 score 0.0 0.11 0.0
SIFT neutral neutral neutral
SIFT score 0.72 0.35 0.81
SIFT4G Tolerated Tolerated Tolerated
SIFT4G score 0.23 0.051 1.0
VEST Neutral Neutral Neutral
VEST pvalue 0.34 0.17 0.42
VEST FDR 0.5 0.45 0.55
Mitoclass.1 neutral neutral neutral
SNPDryad Neutral Neutral Neutral
SNPDryad score 0.34 0.74 0.07
MutationTaster Polymorphism Polymorphism Polymorphism
MutationTaster score 1 1 1
MutationTaster converted rankscore 0.08975 0.08975 0.08975
MutationTaster model complex_aae complex_aae complex_aae
MutationTaster AAE A64T A64P A64S
fathmm Tolerated Tolerated Tolerated
fathmm score 2.71 2.65 2.79
fathmm converted rankscore 0.12055 0.12676 0.11189
AlphaMissense likely_benign ambiguous likely_benign
AlphaMissense score 0.1106 0.4732 0.0943
CADD Neutral Neutral Neutral
CADD score 0.895687 0.764189 -1.028131
CADD phred 10.05 9.241 0.014
PROVEAN Tolerated Tolerated Tolerated
PROVEAN score 0.01 -1.97 1.31
MutationAssessor neutral neutral neutral
MutationAssessor score -0.68 0.58 -0.9
EFIN SP Neutral Neutral Neutral
EFIN SP score 0.764 0.672 0.676
EFIN HD Neutral Neutral Neutral
EFIN HD score 0.738 0.368 0.952
MLC Neutral Neutral Neutral
MLC score 0.27222524 0.27222524 0.27222524
PANTHER score . . .
PhD-SNP score . . .
APOGEE1 Neutral Neutral Neutral
APOGEE1 score 0.46 0.38 0.44
APOGEE2 Benign VUS Benign
APOGEE2 score 0.0252991649228041 0.483325502098256 0.0300959733751049
CAROL neutral neutral neutral
CAROL score 0.28 0.6 0.19
Condel deleterious deleterious deleterious
Condel score 0.86 0.62 0.91
COVEC WMV neutral neutral neutral
COVEC WMV score -6 -6 -6
MtoolBox neutral neutral neutral
MtoolBox DS 0.09 0.26 0.08
DEOGEN2 Tolerated Tolerated Tolerated
DEOGEN2 score 0.005796 0.026009 0.004019
DEOGEN2 converted rankscore 0.05248 0.19333 0.03433
Meta-SNP . . .
Meta-SNP score . . .
PolyPhen2 transf high impact medium impact high impact
PolyPhen2 transf score 2.07 0.1 2.07
SIFT_transf medium impact medium impact medium impact
SIFT transf score 0.51 0.12 0.63
MutationAssessor transf low impact medium impact low impact
MutationAssessor transf score -1.63 -0.2 -1.92
CHASM Neutral Neutral Neutral
CHASM pvalue 0.55 0.37 0.39
CHASM FDR 0.8 0.8 0.8
ClinVar id 692359.0 . .
ClinVar Allele id 680895.0 . .
ClinVar CLNDISDB MONDO:MONDO:0009723,MedGen:C0023264,OMIM:256000,Orphanet:506 . .
ClinVar CLNDN Leigh_syndrome . .
ClinVar CLNSIG Uncertain_significance . .
MITOMAP Disease Clinical info . . LHON
MITOMAP Disease Status . . Reported / Secondary
MITOMAP Disease Hom/Het ./. ./. +/-
MITOMAP General GenBank Freq 0.0131% . 0.018%
MITOMAP General GenBank Seqs 8 . 11
MITOMAP General Curated refs 24448545 . 10520236;16060290;15466285;15972314;29987491;16714301
MITOMAP Variant Class polymorphism . polymorphism;disease
gnomAD 3.1 AN 56428.0 56431.0 56429.0
gnomAD 3.1 AC Homo 3.0 0.0 0.0
gnomAD 3.1 AF Hom 5.31651e-05 0.0 0.0
gnomAD 3.1 AC Het 1.0 0.0 0.0
gnomAD 3.1 AF Het 1.77217e-05 0.0 0.0
gnomAD 3.1 filter PASS npg npg
HelixMTdb AC Hom 6.0 . 16.0
HelixMTdb AF Hom 3.06149e-05 . 8.163974e-05
HelixMTdb AC Het 1.0 . 0.0
HelixMTdb AF Het 5.1024836e-06 . 0.0
HelixMTdb mean ARF 0.86726 . .
HelixMTdb max ARF 0.86726 . .
ToMMo 54KJPN AC . . 610
ToMMo 54KJPN AF . . 0.011233
ToMMo 54KJPN AN . . 54302
COSMIC 90 COSM5653110 . .
dbSNP 156 id rs1603218984 . rs1603218984
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
For more info, please check the output legend.
0
Details:
0
Score:  
0
  [min -20, max 10]
  • Predicted accelerated evolution:  score <= 0
  • Conserved:  score > 0
Score:  
0
  [min -20, max 12]
  • Predicted accelerated evolution:  score <= 0
  • Conserved:  score > 0
Score:  
0
  [min 0, max 1]
  • Non-conserved:  score <= 0.7
  • Conserved:  score > 0.7 (soft threshold)
Score:  
0
  [min 0, max 1]
  • Non-conserved:  score <= 0.7
  • Conserved:  score > 0.7 (soft threshold)
Score:  
0
  [min 0, max 1]
  • Neutral:  score <= 0.15
  • Possibly damaging:  0.15 < score <= 0.85
  • Probably damaging:  score > 0.85
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.05
  • Deleterious:  score <= 0.05
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.05
  • Deleterious:  score <= 0.05
Score:  
0
  [min -16.13, max 10.64]
  • Neutral:  score > 1.5
  • Deleterious:  score <= 1.5
Score:  
0
  [min 0.0, max 1.0]
  • Likely benign:  score <= 0.34
  • Ambiguous:  0.34 < score < 0.56
  • Likely pathogenic:  score >= 0.56
Score:  
0
  [min -14, max 14]
  • Neutral:  score > -2.5
  • Deleterious:  score <= -2.5 (soft threshold)
Score:  
0
  [min -6, max 6]
  • Neutral:  score <= 0.8
  • Low impact:  0.8 < score <= 1.9
  • Medium impact:  1.9 < score <= 3.5
  • High impact:  score > 3.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.6
  • Damaging:  score <= 0.6
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.28
  • Damaging:  score <= 0.28
Phred score:  
0
  [min 0, max Unlimited]
  • Neutral:  score < 20 (soft threshold)
  • Deleterious:  score >= 20
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5 (soft threshold)
  • Deleterious:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Polymorphism:  score < 0.5
  • Disease causing:  score >= 0.5
P-value:  
0
  [min 0, max 1]
  • Neutral:  p-value > 0.05
  • Pathogenic:  p-value <= 0.05
Score:  
0
  [min 0, max 1]
No hard-thresholds were indicated by authors (ref). Indicatively:
  • Neutral:  score < 0.9
  • Pathogenic:  score >= 0.9
No score. Categorical only
Please refer to Additional File 14: Table S10 for further details.
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.98
  • Deleterious:  score >= 0.98
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Deleterious:  score >= 0.5
Score:  
0
  [min -6, max 6]
  • Neutral:  score < 0
  • Deleterious:  score > 0
  • Inaccurate prediction:  score = 0
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Deleterious:  score >= 0.5
DS score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.43
  • Deleterious:  score >= 0.43
Pathogenicity score:  
0
  [min 0, max 1]
  • Neutral:  score ≤ 0.5
  • Pathogenic:  score > 0.5


Pathogenicity score for this variant:  
0
  [min 0, max 1]
ACMG-AMP curations for mitochondrial variants should use the raw scores. Standalone probabilities are shown below:
  • Benign:  score ≤ 0.062 (prob. ≤ 0.001)
  • Likely-benign:  0.062 < score ≤ 0.265 (0.001 < prob. ≤ 0.1)
  • Low-scoring VUS (VUS-):  0.265 < score ≤ 0.396 (0.1 < prob. ≤ 0.33)
  • VUS:  0.396 < score ≤ 0.544 (0.33 < prob. ≤ 0.66)
  • High-scoring VUS (VUS+):  0.544 < score < 0.716 (0.66 < prob. < 0.9)
  • Likely-pathogenic:  0.716 ≤ score < 0.907 (0.9 ≤ prob. < 0.99)
  • Pathogenic:  score ≥ 0.907 (prob. ≥ 0.99)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1 (soft threshold)
  • Medium impact:  -1 < score < 1.5 (soft threshold)
  • High impact:  score >= 1.5 (soft threshold)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1
  • Medium impact:  -1 < score < 2 (soft threshold)
  • High impact:  score >= 2 (soft threshold)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1
  • Medium impact:  -1 < score < 2 (soft threshold)
  • High impact:  score >= 2 (soft threshold)
P-value:  
0
  [min 0, max 1]
  • Neutral:  FDR > 0.2
  • Driver:  FDR <= 0.2
The frequency of a CPD variant is proportional to the
number of aligned orthologous sequences that
carry a specific human pathogenic variant as
wild-type amino acid on the total number of aligned
sequences.

For more info, please check the output legend