chr9-32973574-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001195248.2(APTX):c.953G>A(p.Arg318His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R318C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001195248.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APTX | NM_001195248.2 | c.953G>A | p.Arg318His | missense_variant | 8/8 | ENST00000379817.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APTX | ENST00000379817.7 | c.953G>A | p.Arg318His | missense_variant | 8/8 | 1 | NM_001195248.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000855 AC: 13AN: 152030Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251232Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135764
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461866Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 727238
GnomAD4 genome AF: 0.0000855 AC: 13AN: 152030Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74264
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 17, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 318 of the APTX protein (p.Arg318His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with APTX-related conditions. ClinVar contains an entry for this variant (Variation ID: 286950). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 26, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at