chr7-149874037-C-T

Variant names:

• chr7-149874037-C-T
• rs1563135433
• NM_145230.4:c.-29C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145230.4(ATP6V0E2):​c.-29C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000839 in 1,549,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000086 (0 hom.)
• Consequence: ATP6V0E2 NM_145230.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.928
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09283653).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145230.4. 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
	ATP6V0E2	NM_145230.4	MANE Select	c.-29C>T		5_prime_UTR	Exon 1 of 4	NP_660265.3	Q8NHE4-1
	ATP6V0E2	NM_001289990.2		c.-29C>T		5_prime_UTR	Exon 1 of 4	NP_001276919.2	Q8NHE4-3
	ATP6V0E2	NM_001100592.3		c.-29C>T		5_prime_UTR	Exon 1 of 3	NP_001094062.2	Q8NHE4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V0E2	ENST00000425642.3	TSL:1 MANE Select	c.-29C>T		5_prime_UTR	Exon 1 of 4	ENSP00000396148.2	Q8NHE4-1
	ATP6V0E2	ENST00000421974.7	TSL:1	c.-29C>T		5_prime_UTR	Exon 1 of 3	ENSP00000411672.3	Q8NHE4-2
	ATP6V0E2	ENST00000606024.5	TSL:1	c.-29C>T		5_prime_UTR	Exon 1 of 3	ENSP00000475904.1	Q8NHE4-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000677 AC: 1 AN: 147718 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000859 AC: 12 AN: 1397190 Hom.: 0 Cov.: 31 AF XY: 0.00000580 AC XY: 4 AN XY: 689190

African (AFR) AF: 0.00 AC: 0 AN: 31560

American (AMR) AF: 0.0000280 AC: 1 AN: 35682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25146

East Asian (EAS) AF: 0.00 AC: 0 AN: 35716

South Asian (SAS) AF: 0.00 AC: 0 AN: 79210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000927 AC: 10 AN: 1078570

Other (OTH) AF: 0.0000173 AC: 1 AN: 57950

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152310 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74484

African (AFR) AF: 0.00 AC: 0 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000468 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Uncertain	0.99
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.93
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.050
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.11	T
Polyphen		0.80	P
Vest4		0.12
MutPred		0.21		Loss of glycosylation at P39 (P = 0.1043)
MVP		0.17
MPC		0.21
ClinPred		0.14	T
GERP RS		2.1
PromoterAI		0.32	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.55

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: rs1563135433; hg19: chr7-149571126;