rs1553778909
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PP3_ModeratePP5
The NM_000532.5(PCCB):c.763G>A(p.Gly255Ser) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. 13/23 in silico tools predict a damaging outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G255G) has been classified as Likely benign.
Frequency
Consequence
NM_000532.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCCB | NM_000532.5 | c.763G>A | p.Gly255Ser | missense_variant, splice_region_variant | 7/15 | ENST00000251654.9 | |
PCCB | NM_001178014.2 | c.823G>A | p.Gly275Ser | missense_variant, splice_region_variant | 8/16 | ||
PCCB | XM_011512873.2 | c.763G>A | p.Gly255Ser | missense_variant, splice_region_variant | 7/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCCB | ENST00000251654.9 | c.763G>A | p.Gly255Ser | missense_variant, splice_region_variant | 7/15 | 1 | NM_000532.5 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1387228Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 694666
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Propionic acidemia Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Mar 22, 2018 | - - |
Likely pathogenic, criteria provided, single submitter | in vitro;research | Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics | Feb 17, 2021 | PM1, PM2, PM5, PP2, PP3 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at