dbSNP rs2286241: ATP6V0B:p.Ala19Ala (chr1-43975097-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.515

Publications

0 publications found

Variant links:

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]

ATP6V0B links:

LOC124904167 (HGNC:):

LOC124904167 links:

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new If you want to explore the variant's impact on the transcript NM_004047.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004047.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP6V0B	NM_004047.5	MANE Select	c.57G>A	p.Ala19Ala	synonymous	Exon 1 of 8	NP_004038.1	Q99437-1
ATP6V0B	NM_001294333.2		c.57G>A	p.Ala19Ala	synonymous	Exon 1 of 7	NP_001281262.1	E9PNL3
ATP6V0B	NM_001039457.3		c.-36G>A		5_prime_UTR	Exon 1 of 7	NP_001034546.1	Q99437-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP6V0B	ENST00000472174.7	TSL:1 MANE Select	c.57G>A	p.Ala19Ala	synonymous	Exon 1 of 8	ENSP00000431605.1	Q99437-1
ATP6V0B	ENST00000468183.5	TSL:1	n.127G>A		non_coding_transcript_exon	Exon 1 of 6
ATP6V0B	ENST00000532642.5	TSL:2	c.57G>A	p.Ala19Ala	synonymous	Exon 1 of 7	ENSP00000434729.1	E9PNL3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000159

AC:

AN:

1254974

Hom.:

Cov.:

AF XY:

0.00000164

AC XY:

AN XY:

610572

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

24206

American (AMR)

AF:

0.00

AC:

AN:

14858

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17738

East Asian (EAS)

AF:

0.00

AC:

AN:

28494

South Asian (SAS)

AF:

0.00

AC:

AN:

59986

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4922

European-Non Finnish (NFE)

AF:

0.00000196

AC:

AN:

1018418

Other (OTH)

AF:

0.00

AC:

AN:

51738

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

0.52

PromoterAI

0.10

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Mutation Taster

=298/2

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over