rs2279023

Positions:

• chr16-67444348-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 48 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6V0D1	NM_004691.5	c.481+180C>T		intron_variant		ENST00000290949.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V0D1	ENST00000290949.8	c.481+180C>T		intron_variant		1	NM_004691.5	P1

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3819 AN: 152218 Hom.: 48 Cov.: 33

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.: 48 Cov.: 33 AF XY: 0.0242 AC XY: 1805 AN XY: 74496

Gnomad4 AFR AF: 0.0267

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.00944

Gnomad4 SAS AF: 0.0323

Gnomad4 FIN AF: 0.00895

Gnomad4 NFE AF: 0.0299

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0307 Hom.: 78

Bravo AF: 0.0254

Asia WGS AF: 0.0260 AC: 91 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
DANN	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs2279023; hg19: chr16-67478251;