17-48895761-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_005175.3(ATP5MC1):c.403G>T(p.Ala135Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 69,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Consequence

ATP5MC1
NM_005175.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.97

Publications

4 publications found

Variant links:

Genes affected

ATP5MC1 (HGNC:841): (ATP synthase membrane subunit c locus 1) This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene is one of three genes that encode subunit c of the proton channel. Each of the three genes have distinct mitochondrial import sequences but encode the identical mature protein. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

ATP5MC1 links:

ENSG00000293025 (HGNC:):

ENSG00000293025 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.785

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005175.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP5MC1	NM_005175.3	MANE Select	c.403G>T	p.Ala135Ser	missense	Exon 5 of 5	NP_005166.1	P05496
ATP5MC1	NM_001002027.2		c.403G>T	p.Ala135Ser	missense	Exon 5 of 5	NP_001002027.1	P05496
LOC105371814	NR_135674.1		n.46-3084C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP5MC1	ENST00000393366.7	TSL:1 MANE Select	c.403G>T	p.Ala135Ser	missense	Exon 5 of 5	ENSP00000377033.2	P05496
ATP5MC1	ENST00000355938.9	TSL:1	c.403G>T	p.Ala135Ser	missense	Exon 5 of 5	ENSP00000348205.5	P05496
ATP5MC1	ENST00000938823.1		c.484G>T	p.Ala162Ser	missense	Exon 6 of 6	ENSP00000608882.1

Frequencies

GnomAD3 genomes

AF:

0.0000144

AC:

AN:

69230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000552

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000144

AC:

AN:

69230

Hom.:

Cov.:

AF XY:

0.0000311

AC XY:

AN XY:

32160

show subpopulations

African (AFR)

AF:

0.0000552

AC:

AN:

18102

American (AMR)

AF:

0.00

AC:

AN:

5322

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1934

East Asian (EAS)

AF:

0.00

AC:

AN:

2268

South Asian (SAS)

AF:

0.00

AC:

AN:

1400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3884

Middle Eastern (MID)

AF:

0.00

AC:

AN:

158

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

34892

Other (OTH)

AF:

0.00

AC:

AN:

834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

1.0

M_CAP

Benign

0.027

MetaRNN

Pathogenic

0.79

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.7

PhyloP100

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.27

Sift

Benign

0.040

Sift4G

Benign

0.10

Polyphen

0.95

Vest4

0.82

MutPred

0.56

Gain of disorder (P = 0.0092)

MVP

0.41

MPC

1.5

ClinPred

0.95

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over