NM_004047.5:c.57G>A

Variant names:

• chr1-43975097-G-A
• rs2286241
• NM_004047.5:c.57G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004047.5(ATP6V0B):​c.57G>A​(p.Ala19Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,254,974 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: ATP6V0B NM_004047.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515
• Publications: 0 publications found

Genes affected

ATP6V0B (HGNC:861): (ATPase H+ transporting V0 subunit b) This gene encodes a portion of the V0 domain of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. Activity of this enzyme is necessary for such varied processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

LOC124904167 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=0.515 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V0B	NM_004047.5	c.57G>A	p.Ala19Ala	synonymous_variant	Exon 1 of 8	ENST00000472174.7	NP_004038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V0B	ENST00000472174.7	c.57G>A	p.Ala19Ala	synonymous_variant	Exon 1 of 8	1	NM_004047.5	ENSP00000431605.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000159 AC: 2 AN: 1254974 Hom.: 0 Cov.: 31 AF XY: 0.00000164 AC XY: 1 AN XY: 610572

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24206

American (AMR) AF: 0.00 AC: 0 AN: 14858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17738

East Asian (EAS) AF: 0.00 AC: 0 AN: 28494

South Asian (SAS) AF: 0.00 AC: 0 AN: 59986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4922

European-Non Finnish (NFE) AF: 0.00000196 AC: 2 AN: 1018418

Other (OTH) AF: 0.00 AC: 0 AN: 51738

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.044843), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.97
PhyloP100		0.52
PromoterAI		0.10	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
Mutation Taster		=298/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2286241; hg19: chr1-44440769;