chr17-42494785-G-A

Variant names:

• chr17-42494785-G-A
• rs11651671
• NM_001130021.3:c.1315-249G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378
• Publications: 13 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130021.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V0A1	NM_001130021.3	MANE Select	c.1315-249G>A		intron	N/A	NP_001123493.1
	MIR548AT	NR_049845.1		n.13G>A		non_coding_transcript_exon	Exon 1 of 1
	ATP6V0A1	NM_001378530.1		c.1438-249G>A		intron	N/A	NP_001365459.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V0A1	ENST00000343619.9	TSL:1 MANE Select	c.1315-249G>A		intron	N/A	ENSP00000342951.3
	ATP6V0A1	ENST00000264649.10	TSL:1	c.1336-249G>A		intron	N/A	ENSP00000264649.5
	ATP6V0A1	ENST00000393829.6	TSL:1	c.1315-249G>A		intron	N/A	ENSP00000377415.2

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35676 AN: 151880 Hom.: 4493 Cov.: 31

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

GnomAD2 exomes AF: 0.241 AC: 8572 AN: 35508 AF XY: 0.233

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 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.: 5 AF XY: 0.248 AC XY: 40808 AN XY: 164464

African (AFR) AF: 0.192 AC: 1897 AN: 9876

American (AMR) AF: 0.301 AC: 3485 AN: 11564

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 1942 AN: 10174

East Asian (EAS) AF: 0.00915 AC: 233 AN: 25470

South Asian (SAS) AF: 0.189 AC: 2751 AN: 14536

European-Finnish (FIN) AF: 0.302 AC: 6564 AN: 21736

Middle Eastern (MID) AF: 0.149 AC: 368 AN: 2474

European-Non Finnish (NFE) AF: 0.283 AC: 57991 AN: 205238

Other (OTH) AF: 0.235 AC: 4523 AN: 19210

GnomAD4 genome AF: 0.235 AC: 35687 AN: 151998 Hom.: 4502 Cov.: 31 AF XY: 0.232 AC XY: 17205 AN XY: 74306

African (AFR) AF: 0.182 AC: 7555 AN: 41456

American (AMR) AF: 0.253 AC: 3856 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 668 AN: 3468

East Asian (EAS) AF: 0.0230 AC: 119 AN: 5182

South Asian (SAS) AF: 0.155 AC: 744 AN: 4814

European-Finnish (FIN) AF: 0.297 AC: 3134 AN: 10542

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18990 AN: 67952

Other (OTH) AF: 0.193 AC: 408 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.36
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11651671; hg19: chr17-40646803;