rs138149179
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_000282.4(PCCA):āc.937C>Gā(p.Arg313Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,856 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. R313Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000282.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCCA | NM_000282.4 | c.937C>G | p.Arg313Gly | missense_variant | 12/24 | ENST00000376285.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCCA | ENST00000376285.6 | c.937C>G | p.Arg313Gly | missense_variant | 12/24 | 1 | NM_000282.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460856Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 726762
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Propionic acidemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 04, 2021 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PCCA protein function. This variant has not been reported in the literature in individuals with PCCA-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 313 of the PCCA protein (p.Arg313Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at