chr17-42521703-T-C

Variant names:

• chr17-42521703-T-C
• rs938671
• ENST00000585828.5:n.1260T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000585828.5(ATP6V0A1):​n.1260T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 152,336 control chromosomes in the GnomAD database, including 435 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 0.072 (434 hom., cov: 32)
  • Exomes 𝑓: 0.052 (1 hom.)
• Consequence: ATP6V0A1 ENST00000585828.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 13 publications found

Genes affected

ATP6V0A1 (HGNC:865): (ATPase H+ transporting V0 subunit a1) 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 gene encodes one of three A subunit proteins and the encoded protein is associated with clathrin-coated vesicles. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ATP6V0A1 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy 104

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• neurodevelopmental disorder with epilepsy and brain atrophy

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000585828.5. 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
	ATP6V0A1	NM_001130021.3	MANE Select	c.*583T>C		3_prime_UTR	Exon 22 of 22	NP_001123493.1
	ATP6V0A1	NM_001378530.1		c.*583T>C		3_prime_UTR	Exon 24 of 24	NP_001365459.1
	ATP6V0A1	NM_001378531.1		c.*583T>C		3_prime_UTR	Exon 23 of 23	NP_001365460.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V0A1	ENST00000585828.5	TSL:1	n.1260T>C		non_coding_transcript_exon	Exon 4 of 4
	ATP6V0A1	ENST00000343619.9	TSL:1 MANE Select	c.*583T>C		3_prime_UTR	Exon 22 of 22	ENSP00000342951.3
	ATP6V0A1	ENST00000264649.10	TSL:1	c.*583T>C		3_prime_UTR	Exon 21 of 21	ENSP00000264649.5

Frequencies

GnomAD3 genomes AF: 0.0723 AC: 10979 AN: 151928 Hom.: 433 Cov.: 32

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0722

Gnomad ASJ AF: 0.0721

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0559

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0681

Gnomad OTH AF: 0.0757

GnomAD4 exome AF: 0.0517 AC: 15 AN: 290 Hom.: 1 Cov.: 0 AF XY: 0.0663 AC XY: 13 AN XY: 196

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 0.0588 AC: 8 AN: 136

South Asian (SAS) AF: 0.00 AC: 0 AN: 6

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0373 AC: 5 AN: 134

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0723 AC: 10998 AN: 152046 Hom.: 434 Cov.: 32 AF XY: 0.0721 AC XY: 5361 AN XY: 74326

African (AFR) AF: 0.0694 AC: 2877 AN: 41438

American (AMR) AF: 0.0721 AC: 1102 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0721 AC: 250 AN: 3468

East Asian (EAS) AF: 0.146 AC: 752 AN: 5162

South Asian (SAS) AF: 0.102 AC: 492 AN: 4812

European-Finnish (FIN) AF: 0.0559 AC: 592 AN: 10594

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0681 AC: 4632 AN: 67970

Other (OTH) AF: 0.0778 AC: 164 AN: 2108

Alfa AF: 0.0657 Hom.: 158

Bravo AF: 0.0716

Asia WGS AF: 0.150 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.39
DANN	Benign	0.53
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs938671; hg19: chr17-40673721;