chr9-32973568-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001195248.2(APTX):c.959A>T(p.His320Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,613,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. H320H) has been classified as Likely benign.
Frequency
Consequence
NM_001195248.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APTX | NM_001195248.2 | c.959A>T | p.His320Leu | missense_variant | 8/8 | ENST00000379817.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APTX | ENST00000379817.7 | c.959A>T | p.His320Leu | missense_variant | 8/8 | 1 | NM_001195248.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152032Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251266Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135792
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.0000399 AC XY: 29AN XY: 727246
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152032Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74258
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 16, 2021 | The c.959A>T (p.H320L) alteration is located in exon 9 (coding exon 7) of the APTX gene. This alteration results from a A to T substitution at nucleotide position 959, causing the histidine (H) at amino acid position 320 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 320 of the APTX protein (p.His320Leu). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 1356291). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at