chrX-40580946-G-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000636639.1(ATP6AP2):c.-120G>C variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 897,190 control chromosomes in the GnomAD database, including 100 homozygotes. There are 4,188 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.019 ( 17 hom., 646 hem., cov: 25)
Exomes 𝑓: 0.016 ( 83 hom. 3542 hem. )
Consequence
ATP6AP2
ENST00000636639.1 5_prime_UTR, NMD_transcript
ENST00000636639.1 5_prime_UTR, NMD_transcript
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.367
Genes affected
ATP6AP2 (HGNC:18305): (ATPase H+ transporting accessory protein 2) This gene encodes a protein that is associated with adenosine triphosphatases (ATPases). Proton-translocating ATPases have fundamental roles in energy conservation, secondary active transport, acidification of intracellular compartments, and cellular pH homeostasis. There are three classes of ATPases- F, P, and V. The vacuolar (V-type) ATPases have a transmembrane proton-conducting sector and an extramembrane catalytic sector. The encoded protein has been found associated with the transmembrane sector of the V-type ATPases. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant X-40580946-G-C is Benign according to our data. Variant chrX-40580946-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 670923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0188 (2127/113291) while in subpopulation AFR AF= 0.0251 (785/31294). AF 95% confidence interval is 0.0236. There are 17 homozygotes in gnomad4. There are 646 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 17 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP6AP2 | NM_005765.3 | upstream_gene_variant | ENST00000636580.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP6AP2 | ENST00000636580.2 | upstream_gene_variant | 1 | NM_005765.3 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0188 AC: 2125AN: 113241Hom.: 17 Cov.: 25 AF XY: 0.0182 AC XY: 645AN XY: 35391
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GnomAD3 exomes AF: 0.0146 AC: 1466AN: 100409Hom.: 12 AF XY: 0.0138 AC XY: 501AN XY: 36295
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GnomAD4 exome AF: 0.0156 AC: 12205AN: 783899Hom.: 83 Cov.: 13 AF XY: 0.0164 AC XY: 3542AN XY: 216343
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GnomAD4 genome AF: 0.0188 AC: 2127AN: 113291Hom.: 17 Cov.: 25 AF XY: 0.0182 AC XY: 646AN XY: 35451
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at