3-113778539-C-G

Variant names:

• chr3-113778539-C-G
• rs12631232
• NM_001690.4:c.-13-202C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001690.4(ATP6V1A):​c.-13-202C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,052 control chromosomes in the GnomAD database, including 6,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (6952 hom., cov: 32)
• Consequence: ATP6V1A NM_001690.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.957
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 3-113778539-C-G is Benign according to our data. Variant chr3-113778539-C-G is described in ClinVar as Benign. ClinVar VariationId is 1183335.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 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.-13-202C>G		intron	N/A	NP_001681.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1A	ENST00000273398.8	TSL:1 MANE Select	c.-13-202C>G		intron	N/A	ENSP00000273398.3	P38606-1
	ATP6V1A	ENST00000703904.2		c.-13-202C>G		intron	N/A	ENSP00000515542.1	P38606-1
	ATP6V1A	ENST00000703910.1		c.-13-202C>G		intron	N/A	ENSP00000515547.1	P38606-1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43350 AN: 151934 Hom.: 6955 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.285 AC: 43337 AN: 152052 Hom.: 6952 Cov.: 32 AF XY: 0.287 AC XY: 21333 AN XY: 74294

African (AFR) AF: 0.143 AC: 5954 AN: 41522

American (AMR) AF: 0.235 AC: 3595 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 847 AN: 3470

East Asian (EAS) AF: 0.364 AC: 1878 AN: 5158

South Asian (SAS) AF: 0.201 AC: 969 AN: 4816

European-Finnish (FIN) AF: 0.452 AC: 4754 AN: 10516

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24266 AN: 67970

Other (OTH) AF: 0.274 AC: 580 AN: 2116

Alfa AF: 0.214 Hom.: 540

Bravo AF: 0.264

Asia WGS AF: 0.238 AC: 826 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.44
PhyloP100		-0.96
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: rs12631232; hg19: chr3-113497386;