rs781305219

Variant names:

• chr12-123737251-C-G
• NM_012463.4:c.1018C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-123737251-C-G
• chr12-123737251-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012463.4(ATP6V0A2):​c.1018C>G​(p.Arg340Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ATP6V0A2 NM_012463.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.114417434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V0A2	NM_012463.4	c.1018C>G	p.Arg340Gly	missense_variant	Exon 9 of 20	ENST00000330342.8	NP_036595.2
ATP6V0A2	XM_024448910.2	c.1018C>G	p.Arg340Gly	missense_variant	Exon 9 of 19		XP_024304678.1
ATP6V0A2	XM_024448911.2	c.505C>G	p.Arg169Gly	missense_variant	Exon 5 of 16		XP_024304679.1
ATP6V0A2	XM_024448912.2	c.196C>G	p.Arg66Gly	missense_variant	Exon 2 of 13		XP_024304680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V0A2	ENST00000330342.8	c.1018C>G	p.Arg340Gly	missense_variant	Exon 9 of 20	1	NM_012463.4	ENSP00000332247.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727234

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	14
DANN	Benign	0.61
DEOGEN2	Uncertain	0.54	D;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.87	D;T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.5	L;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.6	D;.;D
REVEL	Benign	0.23
Sift	Benign	0.38	T;.;T
Sift4G	Benign	0.42	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.51
MutPred		0.52		Gain of catalytic residue at Q336 (P = 0.0373);Gain of catalytic residue at Q336 (P = 0.0373);.;
MVP		0.17
MPC		0.35
ClinPred		0.053	T
GERP RS		-2.1
Varity_R		0.094
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-124221798;