rs11539554
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2
The NM_000282.4(PCCA):c.15G>A(p.Trp5*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000736 in 1,359,574 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 Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 7.4e-7 ( 0 hom. )
Consequence
PCCA
NM_000282.4 stop_gained
NM_000282.4 stop_gained
Scores
2
2
2
Clinical Significance
Conservation
PhyloP100: 2.01
Publications
0 publications found
Genes affected
PCCA (HGNC:8653): (propionyl-CoA carboxylase subunit alpha) The protein encoded by this gene is the alpha subunit of the heterodimeric mitochondrial enzyme Propionyl-CoA carboxylase. PCCA encodes the biotin-binding region of this enzyme. Mutations in either PCCA or PCCB (encoding the beta subunit) lead to an enzyme deficiency resulting in propionic acidemia. 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 was made for transcript
Our verdict: Pathogenic. The variant received 10 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 211 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000282.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PCCA | NM_000282.4 | MANE Select | c.15G>A | p.Trp5* | stop_gained | Exon 1 of 24 | NP_000273.2 | P05165-1 | |
| PCCA | NM_001352605.2 | c.15G>A | p.Trp5* | stop_gained | Exon 1 of 23 | NP_001339534.1 | |||
| PCCA | NM_001127692.3 | c.15G>A | p.Trp5* | stop_gained | Exon 1 of 23 | NP_001121164.1 | P05165-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PCCA | ENST00000376285.6 | TSL:1 MANE Select | c.15G>A | p.Trp5* | stop_gained | Exon 1 of 24 | ENSP00000365462.1 | P05165-1 | |
| PCCA | ENST00000881637.1 | c.15G>A | p.Trp5* | stop_gained | Exon 1 of 25 | ENSP00000551696.1 | |||
| PCCA | ENST00000881640.1 | c.15G>A | p.Trp5* | stop_gained | Exon 1 of 25 | ENSP00000551699.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 7.36e-7 AC: 1AN: 1359574Hom.: 0 Cov.: 31 AF XY: 0.00000150 AC XY: 1AN XY: 668212 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1359574
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
668212
show subpopulations
African (AFR)
AF:
AC:
0
AN:
28698
American (AMR)
AF:
AC:
0
AN:
33348
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
23798
East Asian (EAS)
AF:
AC:
1
AN:
32856
South Asian (SAS)
AF:
AC:
0
AN:
73564
European-Finnish (FIN)
AF:
AC:
0
AN:
45432
Middle Eastern (MID)
AF:
AC:
0
AN:
4724
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1060914
Other (OTH)
AF:
AC:
0
AN:
56240
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
-
1
-
Propionic acidemia (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
PhyloP100
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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