dbSNP rs2279023: ATP6V0D1:c.481+180C>T (chr16-67444348-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_004691.5(ATP6V0D1):c.481+180C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 152,336 control chromosomes in the GnomAD database, including 48 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 0.025 ( 48 hom., cov: 33)

Consequence

ATP6V0D1
NM_004691.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.513

Publications

9 publications found

Variant links:

Genes affected

ATP6V0D1 (HGNC:13724): (ATPase H+ transporting V0 subunit d1) 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 encoded protein is known as the D subunit and is found ubiquitously. [provided by RefSeq, Jul 2008]

ATP6V0D1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0251 (3825/152336) while in subpopulation SAS AF = 0.0323 (156/4830). AF 95% confidence interval is 0.0288. There are 48 homozygotes in GnomAd4. There are 1805 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 48 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V0D1	NM_004691.5 link	c.481+180C>T		intron_variant	Intron 3 of 7	ENST00000290949.8	NP_004682.2	P61421

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V0D1	ENST00000290949.8 link	c.481+180C>T		intron_variant	Intron 3 of 7	1	NM_004691.5	ENSP00000290949.3		P61421

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3819

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0268

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0150

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00923

Gnomad SAS

AF:

0.0323

Gnomad FIN

AF:

0.00895

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0299

Gnomad OTH

AF:

0.0277

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0251

AC:

3825

AN:

152336

Hom.:

Cov.:

AF XY:

0.0242

AC XY:

1805

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0267

AC:

1111

AN:

41578

American (AMR)

AF:

0.0150

AC:

230

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0138

AC:

AN:

3472

East Asian (EAS)

AF:

0.00944

AC:

AN:

5188

South Asian (SAS)

AF:

0.0323

AC:

156

AN:

4830

European-Finnish (FIN)

AF:

0.00895

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0299

AC:

2033

AN:

68016

Other (OTH)

AF:

0.0298

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

196

393

589

786

982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0303

Hom.:

103

Bravo

AF:

0.0254

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.4

(source)

DANN

Benign

0.60

PhyloP100

-0.51

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over