16-2519397-TACAAGTGAGCACTGG-T

Position:

• chr16-2519397-TACAAGTGAGCACTGG-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The ENST00000330398.9(ATP6V0C):​c.260_263+11del variant causes a splice donor, splice donor 5th base, coding sequence, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATP6V0C ENST00000330398.9 splice_donor, splice_donor_5th_base, coding_sequence, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.88

Genes affected

ATP6V0C (HGNC:855): (ATPase H+ transporting V0 subunit c) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c", and d. This gene encodes the V0 subunit c. Alternative splicing results in transcript variants. Pseudogenes have been identified on chromosomes 6 and 17. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.39102563 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.7, offset of -3, new splice context is: ctgGTcagg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-2519397-TACAAGTGAGCACTGG-T is Pathogenic according to our data. Variant chr16-2519397-TACAAGTGAGCACTGG-T is described in ClinVar as [Pathogenic]. Clinvar id is 2575311.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V0C	NM_001694.4	c.260_263+11del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	2/3	ENST00000330398.9	NP_001685.1
ATP6V0C	NM_001198569.2	c.260_263+11del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	3/4		NP_001185498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V0C	ENST00000330398.9	c.260_263+11del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	2/3	1	NM_001694.4	ENSP00000329757	P1
ATP6V0C	ENST00000564973.1	c.131_134+11del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	1/2	2		ENSP00000454868
ATP6V0C	ENST00000565223.1	c.131_134+11del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	2/3	3		ENSP00000457782
ATP6V0C	ENST00000568562.1	c.*15_*18+11del		splice_donor_variant, splice_donor_5th_base_variant, 3_prime_UTR_variant, intron_variant	2/3	3		ENSP00000454597

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Epilepsy, early-onset, 3, with or without developmental delay Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr16-2569398;