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

Scores

1
16
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.81
Variant links:
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]

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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 rank MANE Protein UniProt
ATP6V0A2NM_012463.4 linkc.65C>G p.Ala22Gly missense_variant Exon 1 of 20 ENST00000330342.8 NP_036595.2 Q9Y487
ATP6V0A2XM_024448910.2 linkc.65C>G p.Ala22Gly missense_variant Exon 1 of 19 XP_024304678.1
LOC105370042XR_945477.4 linkn.*136G>C downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATP6V0A2ENST00000330342.8 linkc.65C>G p.Ala22Gly missense_variant Exon 1 of 20 1 NM_012463.4 ENSP00000332247.2 Q9Y487

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

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

Other links and lift over

dbSNP: rs916996699; hg19: chr12-124197177; API