13-100111820-ATG-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000282.4(PCCA):​c.184-17_184-16delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,563,578 control chromosomes in the GnomAD database, including 9,092 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1214 hom., cov: 30)
Exomes 𝑓: 0.10 ( 7878 hom. )

Consequence

PCCA
NM_000282.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.885
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 13-100111820-ATG-A is Benign according to our data. Variant chr13-100111820-ATG-A is described in ClinVar as [Benign]. Clinvar id is 196244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-100111820-ATG-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCCANM_000282.4 linkc.184-17_184-16delGT intron_variant Intron 2 of 23 ENST00000376285.6 NP_000273.2 P05165-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCCAENST00000376285.6 linkc.184-20_184-19delTG intron_variant Intron 2 of 23 1 NM_000282.4 ENSP00000365462.1 P05165-1

Frequencies

GnomAD3 genomes
AF:
0.118
AC:
17897
AN:
151908
Hom.:
1212
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.179
Gnomad AMI
AF:
0.0789
Gnomad AMR
AF:
0.104
Gnomad ASJ
AF:
0.128
Gnomad EAS
AF:
0.00116
Gnomad SAS
AF:
0.104
Gnomad FIN
AF:
0.0589
Gnomad MID
AF:
0.177
Gnomad NFE
AF:
0.102
Gnomad OTH
AF:
0.132
GnomAD3 exomes
AF:
0.0929
AC:
22682
AN:
244140
Hom.:
1230
AF XY:
0.0949
AC XY:
12515
AN XY:
131902
show subpopulations
Gnomad AFR exome
AF:
0.173
Gnomad AMR exome
AF:
0.0699
Gnomad ASJ exome
AF:
0.139
Gnomad EAS exome
AF:
0.000443
Gnomad SAS exome
AF:
0.114
Gnomad FIN exome
AF:
0.0564
Gnomad NFE exome
AF:
0.100
Gnomad OTH exome
AF:
0.112
GnomAD4 exome
AF:
0.0995
AC:
140483
AN:
1411550
Hom.:
7878
AF XY:
0.0997
AC XY:
70282
AN XY:
704592
show subpopulations
Gnomad4 AFR exome
AF:
0.183
Gnomad4 AMR exome
AF:
0.0734
Gnomad4 ASJ exome
AF:
0.140
Gnomad4 EAS exome
AF:
0.000534
Gnomad4 SAS exome
AF:
0.113
Gnomad4 FIN exome
AF:
0.0579
Gnomad4 NFE exome
AF:
0.101
Gnomad4 OTH exome
AF:
0.108
GnomAD4 genome
AF:
0.118
AC:
17933
AN:
152028
Hom.:
1214
Cov.:
30
AF XY:
0.115
AC XY:
8560
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.180
Gnomad4 AMR
AF:
0.104
Gnomad4 ASJ
AF:
0.128
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.105
Gnomad4 FIN
AF:
0.0589
Gnomad4 NFE
AF:
0.102
Gnomad4 OTH
AF:
0.131
Alfa
AF:
0.114
Hom.:
194
Bravo
AF:
0.123
Asia WGS
AF:
0.0570
AC:
196
AN:
3464

ClinVar

Significance: Benign
Submissions summary: Benign:12
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:8
-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Dec 02, 2014
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Nov 10, 2016
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Oct 17, 2019
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Variant summary: PCCA c.184-17_184-16delGT alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.093 in 244140 control chromosomes in the gnomAD database, including 1230 homozygotes. The observed variant frequency is approximately 27-folds over the estimated maximal expected allele frequency for a pathogenic variant in PCCA causing Propionic Acidemia phenotype (0.0034), strongly suggesting that the variant is benign. Two ClinVar submissions (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -

-
Clinical Genetics, Academic Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Apr 04, 2014
GeneDx
Significance: Benign
Review Status: flagged submission
Collection Method: clinical testing

The variant is found in UCD-MET panel(s). -

Feb 23, 2016
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Propionic acidemia Benign:4
Nov 21, 2024
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Sep 16, 2020
Natera, Inc.
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Jan 01, 2011
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: research

- -

Feb 04, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs111778723; hg19: chr13-100764074; API