chr7-149874025-T-A

Position:

• chr7-149874025-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000425642.3(ATP6V0E2):​c.-41T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATP6V0E2 ENST00000425642.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.08

Genes affected

ATP6V0E2 (HGNC:21723): (ATPase H+ transporting V0 subunit e2) Multisubunit vacuolar-type proton pumps, or H(+)-ATPases, acidify various intracellular compartments, such as vacuoles, clathrin-coated and synaptic vesicles, endosomes, lysosomes, and chromaffin granules. H(+)-ATPases are also found in plasma membranes of specialized cells, where they play roles in urinary acidification, bone resorption, and sperm maturation. Multiple subunits form H(+)-ATPases, with proteins of the V1 class hydrolyzing ATP for energy to transport H+, and proteins of the V0 class forming an integral membrane domain through which H+ is transported. ATP6V0E2 encodes an isoform of the H(+)-ATPase V0 e subunit, an essential proton pump component (Blake-Palmer et al., 2007 [PubMed 17350184]).[supplied by OMIM, Mar 2008]

ATP6V0E2-AS1 (HGNC:44180): (ATP6V0E2 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052191377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V0E2	NM_145230.4	c.-41T>A		5_prime_UTR_variant	1/4	ENST00000425642.3	NP_660265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V0E2	ENST00000425642.3	c.-41T>A		5_prime_UTR_variant	1/4	1	NM_145230.4	ENSP00000396148	P1
ATP6V0E2-AS1	ENST00000464939.1	n.243-2229A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2024

The c.107T>A (p.L36Q) alteration is located in exon 1 (coding exon 1) of the ATP6V0E2 gene. This alteration results from a T to A substitution at nucleotide position 107, causing the leucine (L) at amino acid position 36 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.057
DANN	Benign	0.56
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0063	N
LIST_S2	Benign	0.37	T;.;.;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.052	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.40	.;N;N;.
REVEL	Benign	0.023
Sift	Benign	0.036	.;D;T;.
Sift4G	Benign	0.16	T;T;T;T
Polyphen		0.0010	B;B;.;.
Vest4		0.054
MutPred		0.29		Gain of disorder (P = 0.0136);Gain of disorder (P = 0.0136);Gain of disorder (P = 0.0136);Gain of disorder (P = 0.0136);
MVP		0.076
MPC		0.20
ClinPred		0.075	T
GERP RS		-7.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.56

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-149571114;