Variant 2-10775038-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001039362.2(ATP6V1C2):c.792G>A(p.Met264Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000162 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ATP6V1C2
NM_001039362.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12

Variant links:

Genes affected

ATP6V1C2 (HGNC:18264): (ATPase H+ transporting V1 subunit C2) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A,three B, and two G subunits, as well as a C, D, E, F, and H subunit. The V1 domain contains the ATP catalytic site. This gene encodes alternate transcriptional splice variants, encoding different V1 domain C subunit isoforms. [provided by RefSeq, Jul 2008]

ATP6V1C2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6V1C2	NM_001039362.2 linkuse as main transcript	c.792G>A	p.Met264Ile	missense_variant	10/14	ENST00000272238.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V1C2	ENST00000272238.9 linkuse as main transcript	c.792G>A	p.Met264Ile	missense_variant	10/14	5	NM_001039362.2		Q8NEY4-1
ATP6V1C2	ENST00000635370.1 linkuse as main transcript	c.822G>A	p.Met274Ile	missense_variant	10/14	5
ATP6V1C2	ENST00000381661.3 linkuse as main transcript	c.792G>A	p.Met264Ile	missense_variant	10/13	2		P1	Q8NEY4-2
ATP6V1C2	ENST00000648362.1 linkuse as main transcript	c.792G>A	p.Met264Ile	missense_variant	10/12

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000119

AC:

AN:

251346

Hom.:

AF XY:

0.000147

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000170

AC:

248

AN:

1461764

Hom.:

Cov.:

AF XY:

0.000195

AC XY:

142

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000189

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000902

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2022

The c.792G>A (p.M264I) alteration is located in exon 10 (coding exon 9) of the ATP6V1C2 gene. This alteration results from a G to A substitution at nucleotide position 792, causing the methionine (M) at amino acid position 264 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.0048

.;T;.;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.055

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.73

T;T;T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.080

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

.;N;N;.

MutationTaster

Benign

0.97

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.19

.;N;N;.

REVEL

Benign

0.10

Sift

Benign

0.58

.;T;T;.

Sift4G

Benign

0.45

.;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.35, 0.32, 0.30

MutPred

0.53

Loss of MoRF binding (P = 0.1915);Loss of MoRF binding (P = 0.1915);Loss of MoRF binding (P = 0.1915);.;

MVP

0.26

MPC

0.20

ClinPred

0.063

GERP RS

5.7

Varity_R

0.17

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.22

Position offset: 33

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over