chr7-149874034-C-T

Variant names:

• chr7-149874034-C-T
• rs1400776035
• NM_145230.4:c.-32C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145230.4(ATP6V0E2):​c.-32C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,397,150 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ATP6V0E2 NM_145230.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07861191).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V0E2	NM_145230.4	c.-32C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	ENST00000425642.3	NP_660265.3
ATP6V0E2	NM_145230.4	c.-32C>T		5_prime_UTR_variant	Exon 1 of 4	ENST00000425642.3	NP_660265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V0E2	ENST00000425642	c.-32C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	1	NM_145230.4	ENSP00000396148.2
ATP6V0E2	ENST00000425642	c.-32C>T		5_prime_UTR_variant	Exon 1 of 4	1	NM_145230.4	ENSP00000396148.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1397150 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2 AN XY: 689160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.1
DANN	Benign	0.94
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.60	T;.;.;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.079	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.0	.;N;N;.
REVEL	Benign	0.024
Sift	Uncertain	0.0010	.;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.0010	B;B;.;.
Vest4		0.093
MutPred		0.47		Loss of glycosylation at P39 (P = 0.0391);Loss of glycosylation at P39 (P = 0.0391);Loss of glycosylation at P39 (P = 0.0391);Loss of glycosylation at P39 (P = 0.0391);
MVP		0.072
MPC		0.57
ClinPred		0.57	D
GERP RS		-6.6
gMVP		0.53

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

LitVar

Other links and lift over

dbSNP: rs1400776035; hg19: chr7-149571123;