NM_012463.4:c.65C>G

Variant names:

• chr12-123712630-C-G
• rs916996699
• NM_012463.4:c.65C>G

Variant summary

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

The NM_012463.4(ATP6V0A2):​c.65C>G​(p.Ala22Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A22V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATP6V0A2 NM_012463.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81

Genes affected

ATP6V0A2 (HGNC:18481): (ATPase H+ transporting V0 subunit a2) The protein encoded by this gene is a subunit of the vacuolar ATPase (v-ATPase), an heteromultimeric enzyme that is present in intracellular vesicles and in the plasma membrane of specialized cells, and which is essential for the acidification of diverse cellular components. V-ATPase is comprised of a membrane peripheral V(1) domain for ATP hydrolysis, and an integral membrane V(0) domain for proton translocation. The subunit encoded by this gene is a component of the V(0) domain. Mutations in this gene are a cause of both cutis laxa type II and wrinkly skin syndrome. [provided by RefSeq, Jul 2009]

LOC105370042 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
ATP6V0A2	NM_012463.4	c.65C>G	p.Ala22Gly	missense_variant	Exon 1 of 20	ENST00000330342.8	NP_036595.2
ATP6V0A2	XM_024448910.2	c.65C>G	p.Ala22Gly	missense_variant	Exon 1 of 19		XP_024304678.1
LOC105370042	XR_945477.4	n.*136G>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V0A2	ENST00000330342.8	c.65C>G	p.Ala22Gly	missense_variant	Exon 1 of 20	1	NM_012463.4	ENSP00000332247.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.95	D;T
M_CAP	Pathogenic	0.47	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Uncertain	0.72	D
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.4	D;.
REVEL	Uncertain	0.63
Sift	Uncertain	0.010	D;.
Sift4G	Uncertain	0.042	D;D
Polyphen		1.0	D;D
Vest4		0.45
MutPred		0.68		Gain of catalytic residue at T21 (P = 6e-04);Gain of catalytic residue at T21 (P = 6e-04);
MVP		0.63
MPC		0.32
ClinPred		0.99	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.57
gMVP		0.60

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

LitVar

Other links and lift over

dbSNP: rs916996699; hg19: chr12-124197177;