GeneBe

NM_000282.4:c.1855C>A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000282.4(PCCA):​c.1855C>A​(p.Arg619Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000144 in 1,386,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PCCA
NM_000282.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.94

Publications

0 publications found
Variant links:
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]
PCCA Gene-Disease associations (from GenCC):
  • propionic acidemia
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, ClinGen, Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.17).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCCANM_000282.4 linkc.1855C>A p.Arg619Arg synonymous_variant Exon 21 of 24 ENST00000376285.6 NP_000273.2 P05165-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCCAENST00000376285.6 linkc.1855C>A p.Arg619Arg synonymous_variant Exon 21 of 24 1 NM_000282.4 ENSP00000365462.1 P05165-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000144
AC:
2
AN:
1386038
Hom.:
0
Cov.:
26
AF XY:
0.00
AC XY:
0
AN XY:
684480
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
31326
American (AMR)
AF:
0.00
AC:
0
AN:
35608
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25080
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35608
South Asian (SAS)
AF:
0.00
AC:
0
AN:
78824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49244
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5676
European-Non Finnish (NFE)
AF:
0.00000187
AC:
2
AN:
1067214
Other (OTH)
AF:
0.00
AC:
0
AN:
57458
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.17
CADD
Benign
10
DANN
Benign
0.65
PhyloP100
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs1194679272; hg19: chr13-101101515; API