Variant 2-10764370-T-G 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.323T>G(p.Met108Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,780 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ATP6V1C2
NM_001039362.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.40

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:

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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	Protein	UniProt
ATP6V1C2	NM_001039362.2 link	c.323T>G	p.Met108Arg	missense_variant	5/14	ENST00000272238.9	NP_001034451.1	Q8NEY4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATP6V1C2	ENST00000272238.9 link	c.323T>G	p.Met108Arg	missense_variant	5/14	5	NM_001039362.2	ENSP00000272238.4	Q8NEY4-1
ATP6V1C2	ENST00000635370.1 link	c.353T>G	p.Met118Arg	missense_variant	5/14	5		ENSP00000489280.1	A0A0U1RR16
ATP6V1C2	ENST00000381661.3 link	c.323T>G	p.Met108Arg	missense_variant	5/13	2		ENSP00000371077.3	Q8NEY4-2
ATP6V1C2	ENST00000648362.1 link	c.323T>G	p.Met108Arg	missense_variant	5/12			ENSP00000497038.1	A0A3B3IRZ7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461780

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 30, 2024

The c.323T>G (p.M108R) alteration is located in exon 5 (coding exon 4) of the ATP6V1C2 gene. This alteration results from a T to G substitution at nucleotide position 323, causing the methionine (M) at amino acid position 108 to be replaced by an arginine (R). 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

0.17

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.090

.;T;.;.

Eigen

Benign

0.082

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Benign

0.0087

MetaRNN

Uncertain

0.43

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;L;L;.

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-4.1

.;D;D;.

REVEL

Benign

0.25

Sift

Benign

0.47

.;T;T;.

Sift4G

Benign

0.53

.;T;T;T

Polyphen

0.022, 0.018

.;B;B;.

Vest4

0.84, 0.81, 0.80

MutPred

0.49

Gain of solvent accessibility (P = 0.0171);Gain of solvent accessibility (P = 0.0171);Gain of solvent accessibility (P = 0.0171);.;

MVP

0.46

MPC

0.29

ClinPred

0.88

GERP RS

5.7

Varity_R

0.84

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.20

Position offset: -39

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over