rs786200983

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_000532.5(PCCB):​c.990delT​(p.Phe330LeufsTer18) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in Lovd as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 31)

Consequence

PCCB
NM_000532.5 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.45
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-136316958-AT-A is Pathogenic according to our data. Variant chr3-136316958-AT-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCCBNM_000532.5 linkc.990delT p.Phe330LeufsTer18 frameshift_variant Exon 10 of 15 ENST00000251654.9 NP_000523.2 P05166-1
PCCBNM_001178014.2 linkc.1050delT p.Phe350LeufsTer18 frameshift_variant Exon 11 of 16 NP_001171485.1 P05166-2
PCCBXM_011512873.2 linkc.990delT p.Phe330LeufsTer18 frameshift_variant Exon 10 of 11 XP_011511175.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCCBENST00000251654.9 linkc.990delT p.Phe330LeufsTer18 frameshift_variant Exon 10 of 15 1 NM_000532.5 ENSP00000251654.4 P05166-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.23
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.23
Position offset: -17

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs786200983; hg19: chr3-136035800; API