dbSNP rs11651671: ATP6V0A1:c.1315-249G>A (chr17-42494785-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001130021.3(ATP6V0A1):c.1315-249G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 472,276 control chromosomes in the GnomAD database, including 15,842 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4502 hom., cov: 31)

Exomes 𝑓: 0.25 ( 11340 hom. )

Consequence

ATP6V0A1
NM_001130021.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.378

Variant links:

Genes affected

ATP6V0A1 (HGNC:865): (ATPase H+ transporting V0 subunit a1) 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 and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c", and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This gene encodes one of three A subunit proteins and the encoded protein is associated with clathrin-coated vesicles. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ATP6V0A1 links:

MIR548AT (HGNC:43517): (microRNA 548at) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR548AT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V0A1	NM_001130021.3 link	c.1315-249G>A		intron_variant	Intron 12 of 21	ENST00000343619.9	NP_001123493.1	Q93050-2Q53X12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V0A1	ENST00000343619.9 link	c.1315-249G>A		intron_variant	Intron 12 of 21	1	NM_001130021.3	ENSP00000342951.3		Q93050-2

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35676

AN:

151880

Hom.:

4493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.252

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.0229

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.196

GnomAD3 exomes

AF:

0.241

AC:

8572

AN:

35508

Hom.:

1240

AF XY:

0.233

AC XY:

4281

AN XY:

18372

show subpopulations

Gnomad AFR exome

AF:

0.205

Gnomad AMR exome

AF:

0.323

Gnomad ASJ exome

AF:

0.203

Gnomad EAS exome

AF:

0.0157

Gnomad SAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.324

Gnomad NFE exome

AF:

0.302

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.249

AC:

79754

AN:

320278

Hom.:

11340

Cov.:

AF XY:

0.248

AC XY:

40808

AN XY:

164464

show subpopulations

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.301

Gnomad4 ASJ exome

AF:

0.191

Gnomad4 EAS exome

AF:

0.00915

Gnomad4 SAS exome

AF:

0.189

Gnomad4 FIN exome

AF:

0.302

Gnomad4 NFE exome

AF:

0.283

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.235

AC:

35687

AN:

151998

Hom.:

4502

Cov.:

AF XY:

0.232

AC XY:

17205

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.182

Gnomad4 AMR

AF:

0.253

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.0230

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.297

Gnomad4 NFE

AF:

0.279

Gnomad4 OTH

AF:

0.193

Alfa

AF:

0.264

Hom.:

1521

Bravo

AF:

0.231

Asia WGS

AF:

0.0860

AC:

302

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.1

DANN

Benign

0.36

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over