rs202247819
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PP3_StrongPP5_Very_Strong
The NM_000532.5(PCCB):c.457G>C(p.Ala153Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,182 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 Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. A153A) has been classified as Likely benign.
Frequency
Consequence
NM_000532.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCCB | NM_000532.5 | c.457G>C | p.Ala153Pro | missense_variant | 5/15 | ENST00000251654.9 | |
PCCB | NM_001178014.2 | c.517G>C | p.Ala173Pro | missense_variant | 6/16 | ||
PCCB | XM_011512873.2 | c.457G>C | p.Ala153Pro | missense_variant | 5/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCCB | ENST00000251654.9 | c.457G>C | p.Ala153Pro | missense_variant | 5/15 | 1 | NM_000532.5 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 7.10e-7 AC: 1AN: 1408182Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 695280
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Propionic acidemia Pathogenic:2Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 153 of the PCCB protein (p.Ala153Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with propionic acidemia (PMID: 15059621, 35331292). ClinVar contains an entry for this variant (Variation ID: 38884). 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 PCCB protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 11, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at