chr4-105369738-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_176869.3(PPA2):āc.992T>Gā(p.Phe331Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000625 in 1,440,312 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F331L) has been classified as Uncertain significance.
Frequency
Consequence
NM_176869.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPA2 | NM_176869.3 | c.992T>G | p.Phe331Cys | missense_variant | 12/12 | ENST00000341695.10 | |
PPA2 | NM_006903.4 | c.905T>G | p.Phe302Cys | missense_variant | 11/11 | ||
PPA2 | NM_176866.2 | c.686T>G | p.Phe229Cys | missense_variant | 8/8 | ||
PPA2 | NM_176867.3 | c.494T>G | p.Phe165Cys | missense_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPA2 | ENST00000341695.10 | c.992T>G | p.Phe331Cys | missense_variant | 12/12 | 1 | NM_176869.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251158Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135720
GnomAD4 exome AF: 0.00000625 AC: 9AN: 1440312Hom.: 0 Cov.: 31 AF XY: 0.00000697 AC XY: 5AN XY: 717650
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 08, 2022 | 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. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals affected with PPA2-related conditions. This variant is present in population databases (rs371782506, gnomAD 0.0009%). This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 331 of the PPA2 protein (p.Phe331Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at