chr16-67444348-G-A

Variant names:

• chr16-67444348-G-A
• rs2279023
• NM_004691.5:c.481+180C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004691.5. 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
	ATP6V0D1	NM_004691.5	MANE Select	c.481+180C>T		intron	N/A	NP_004682.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V0D1	ENST00000290949.8	TSL:1 MANE Select	c.481+180C>T		intron	N/A	ENSP00000290949.3
	ATP6V0D1	ENST00000540149.5	TSL:2	c.604+180C>T		intron	N/A	ENSP00000441282.1
	ATP6V0D1	ENST00000565835.5	TSL:3	c.122-1170C>T		intron	N/A	ENSP00000463328.1

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

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: 48 AN: 3472

East Asian (EAS) AF: 0.00944 AC: 49 AN: 5188

South Asian (SAS) AF: 0.0323 AC: 156 AN: 4830

European-Finnish (FIN) AF: 0.00895 AC: 95 AN: 10618

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0299 AC: 2033 AN: 68016

Other (OTH) AF: 0.0298 AC: 63 AN: 2116

Alfa AF: 0.0303 Hom.: 103

Bravo AF: 0.0254

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.60
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2279023; hg19: chr16-67478251;