rs202247821
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4_SupportingPP5
The NM_000532.5(PCCB):c.1538_1540dup(p.Ala513_Arg514insPro) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. A513A) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
PCCB
NM_000532.5 inframe_insertion
NM_000532.5 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.71
Genes affected
PCCB (HGNC:8654): (propionyl-CoA carboxylase subunit beta) The protein encoded by this gene is a subunit of the propionyl-CoA carboxylase (PCC) enzyme, which is involved in the catabolism of propionyl-CoA. PCC is a mitochondrial enzyme that probably acts as a dodecamer of six alpha subunits and six beta subunits. This gene encodes the beta subunit of PCC. Defects in this gene are a cause of propionic acidemia type II (PA-2). Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM1
?
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 4 uncertain in NM_000532.5
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_000532.5. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 3-136329943-G-GCCC is Pathogenic according to our data. Variant chr3-136329943-G-GCCC is described in ClinVar as [Pathogenic]. Clinvar id is 12017.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCCB | NM_000532.5 | c.1538_1540dup | p.Ala513_Arg514insPro | inframe_insertion | 15/15 | ENST00000251654.9 | |
PCCB | NM_001178014.2 | c.1598_1600dup | p.Ala533_Arg534insPro | inframe_insertion | 16/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCCB | ENST00000251654.9 | c.1538_1540dup | p.Ala513_Arg514insPro | inframe_insertion | 15/15 | 1 | NM_000532.5 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Propionic acidemia Pathogenic:1Other:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2000 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at