3-113811364-T-C

Variant names:

• chr3-113811364-T-C
• rs12736
• NM_001690.4:c.*1937T>C

Variant summary

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

The NM_001690.4(ATP6V1A):​c.*1937T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,440 control chromosomes in the GnomAD database, including 9,709 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 0.35 (9661 hom., cov: 32)
  • Exomes 𝑓: 0.48 (48 hom.)
• Consequence: ATP6V1A NM_001690.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• Publications: 11 publications found

Genes affected

ATP6V1A (HGNC:851): (ATPase H+ transporting V1 subunit A) 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 one of two V1 domain A subunit isoforms and is found in all tissues. Transcript variants derived from alternative polyadenylation exist. [provided by RefSeq, Jul 2008]

ATP6V1A Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy 93

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive cutis laxa type 2D

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive cutis laxa type 2, classic type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001690.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1A	NM_001690.4	MANE Select	c.*1937T>C		3_prime_UTR	Exon 15 of 15	NP_001681.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1A	ENST00000273398.8	TSL:1 MANE Select	c.*1937T>C		3_prime_UTR	Exon 15 of 15	ENSP00000273398.3	P38606-1
	ATP6V1A	ENST00000703910.1		c.*1937T>C		3_prime_UTR	Exon 16 of 16	ENSP00000515547.1	P38606-1
	ATP6V1A	ENST00000496747.6	TSL:5	c.*1937T>C		3_prime_UTR	Exon 15 of 15	ENSP00000417545.2	C9JA17

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53762 AN: 151888 Hom.: 9648 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.332

GnomAD4 exome AF: 0.477 AC: 207 AN: 434 Hom.: 48 Cov.: 0 AF XY: 0.454 AC XY: 119 AN XY: 262

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.467 AC: 198 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 4 AN: 4

Other (OTH) AF: 0.833 AC: 5 AN: 6

GnomAD4 genome AF: 0.354 AC: 53804 AN: 152006 Hom.: 9661 Cov.: 32 AF XY: 0.354 AC XY: 26288 AN XY: 74290

African (AFR) AF: 0.382 AC: 15842 AN: 41474

American (AMR) AF: 0.263 AC: 4020 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3464

East Asian (EAS) AF: 0.358 AC: 1851 AN: 5168

South Asian (SAS) AF: 0.194 AC: 934 AN: 4818

European-Finnish (FIN) AF: 0.451 AC: 4766 AN: 10556

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24346 AN: 67942

Other (OTH) AF: 0.327 AC: 687 AN: 2104

Alfa AF: 0.355 Hom.: 2502

Bravo AF: 0.343

Asia WGS AF: 0.253 AC: 876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.53
PhyloP100		-0.053
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: rs12736; hg19: chr3-113530211; COSMIC: COSV56364331; COSMIC: COSV56364331;