7-149874127-GC-AT

Variant names:

• chr7-149874127-GC-AT
• NM_145230.4:c.62_63delGCinsAT
• ATP6V0E2 p.Gly21Asp

Variant summary

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

The NM_145230.4(ATP6V0E2):​c.62_63delGCinsAT​(p.Gly21Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G21V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP6V0E2 NM_145230.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.18
• 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.

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.62_63delGCinsAT	p.Gly21Asp	missense	N/A	NP_660265.3	Q8NHE4-1
	ATP6V0E2	NM_001289990.2		c.62_63delGCinsAT	p.Gly21Asp	missense	N/A	NP_001276919.2	Q8NHE4-3
	ATP6V0E2	NM_001100592.3		c.62_63delGCinsAT	p.Gly21Asp	missense	N/A	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.62_63delGCinsAT	p.Gly21Asp	missense	N/A	ENSP00000396148.2	Q8NHE4-1
	ATP6V0E2	ENST00000421974.7	TSL:1	c.62_63delGCinsAT	p.Gly21Asp	missense	N/A	ENSP00000411672.3	Q8NHE4-2
	ATP6V0E2	ENST00000606024.5	TSL:1	c.62_63delGCinsAT	p.Gly21Asp	missense	N/A	ENSP00000475904.1	Q8NHE4-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-149571216;