7-149874004-C-G

Variant names:

• chr7-149874004-C-G
• rs1467395486
• NM_145230.4:c.-62C>G

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.-62C>G 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATP6V0E2 NM_145230.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.561
• 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=0.096426696).

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.-62C>G		5_prime_UTR	Exon 1 of 4	NP_660265.3	Q8NHE4-1
	ATP6V0E2	NM_001289990.2		c.-62C>G		5_prime_UTR	Exon 1 of 4	NP_001276919.2	Q8NHE4-3
	ATP6V0E2	NM_001100592.3		c.-62C>G		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.-62C>G		5_prime_UTR	Exon 1 of 4	ENSP00000396148.2	Q8NHE4-1
	ATP6V0E2	ENST00000421974.7	TSL:1	c.-62C>G		5_prime_UTR	Exon 1 of 3	ENSP00000411672.3	Q8NHE4-2
	ATP6V0E2	ENST00000606024.5	TSL:1	c.-62C>G		5_prime_UTR	Exon 1 of 3	ENSP00000475904.1	Q8NHE4-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.0
DANN	Uncertain	0.99
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.56
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.033
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.12	B
Vest4		0.23
MutPred		0.34		Gain of MoRF binding (P = 0.0021)
MVP		0.39
MPC		0.25
ClinPred		0.39	T
GERP RS		-0.50
PromoterAI		0.34	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.70

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: rs1467395486; hg19: chr7-149571093;