3-136250377-T-G
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate
The NM_000532.5(PCCB):āc.2T>Gā(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,374,114 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 (ā ).
Frequency
Consequence
NM_000532.5 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCCB | NM_000532.5 | c.2T>G | p.Met1? | start_lost | 1/15 | ENST00000251654.9 | |
PCCB | NM_001178014.2 | c.2T>G | p.Met1? | start_lost | 1/16 | ||
PCCB | XM_011512873.2 | c.2T>G | p.Met1? | start_lost | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCCB | ENST00000251654.9 | c.2T>G | p.Met1? | start_lost | 1/15 | 1 | NM_000532.5 | P2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 7.28e-7 AC: 1AN: 1374114Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 674266
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Propionic acidemia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 19, 2023 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PCCB protein in which other variant(s) (p.His59Gln) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with PCCB-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the PCCB mRNA. The next in-frame methionine is located at codon 84. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.