7-149875609-C-T

Variant names:

• chr7-149875609-C-T
• NM_145230.4:c.116C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_145230.4(ATP6V0E2):​c.116C>T​(p.Thr39Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ATP6V0E2 NM_145230.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.54

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V0E2	NM_145230.4	c.116C>T	p.Thr39Ile	missense_variant	Exon 2 of 4	ENST00000425642.3	NP_660265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V0E2	ENST00000425642.3	c.116C>T	p.Thr39Ile	missense_variant	Exon 2 of 4	1	NM_145230.4	ENSP00000396148.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461630 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727086

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.263C>T (p.T88I) alteration is located in exon 2 (coding exon 2) of the ATP6V0E2 gene. This alteration results from a C to T substitution at nucleotide position 263, causing the threonine (T) at amino acid position 88 to be replaced by an isoleucine (I). 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
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;.;.;.;.;.;T;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D;.;.;D;D;D;.;D
M_CAP	Benign	0.025	D
MetaRNN	Pathogenic	0.79	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.14	D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.3	.;D;D;.;D;.;.;D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0070	.;D;D;.;D;.;.;D
Sift4G	Uncertain	0.036	D;D;T;T;T;T;T;T
Polyphen		1.0	D;D;.;.;P;.;D;D
Vest4		0.83
MutPred		0.49		Loss of catalytic residue at T88 (P = 0.0508);Loss of catalytic residue at T88 (P = 0.0508);Loss of catalytic residue at T88 (P = 0.0508);Loss of catalytic residue at T88 (P = 0.0508);.;.;.;.;
MVP		0.49
MPC		0.77
ClinPred		0.97	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
gMVP		0.85

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: chr7-149572698;