13-100268802-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000282.4(PCCA):​c.914+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,558,632 control chromosomes in the GnomAD database, including 760,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 66742 hom., cov: 32)
Exomes 𝑓: 0.99 ( 694011 hom. )

Consequence

PCCA
NM_000282.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.760
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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 13-100268802-A-G is Benign according to our data. Variant chr13-100268802-A-G is described in ClinVar as [Benign]. Clinvar id is 92765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-100268802-A-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCCANM_000282.4 linkc.914+19A>G intron_variant Intron 11 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.914+19A>G intron_variant Intron 11 of 23 1 NM_000282.4 ENSP00000365462.1 P05165-1

Frequencies

GnomAD3 genomes
AF:
0.931
AC:
141552
AN:
152124
Hom.:
66706
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.759
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.971
Gnomad ASJ
AF:
0.999
Gnomad EAS
AF:
1.00
Gnomad SAS
AF:
0.999
Gnomad FIN
AF:
1.00
Gnomad MID
AF:
0.984
Gnomad NFE
AF:
0.999
Gnomad OTH
AF:
0.956
GnomAD2 exomes
AF:
0.981
AC:
245829
AN:
250532
AF XY:
0.986
show subpopulations
Gnomad AFR exome
AF:
0.751
Gnomad AMR exome
AF:
0.986
Gnomad ASJ exome
AF:
0.999
Gnomad EAS exome
AF:
1.00
Gnomad FIN exome
AF:
1.00
Gnomad NFE exome
AF:
0.999
Gnomad OTH exome
AF:
0.990
GnomAD4 exome
AF:
0.993
AC:
1396161
AN:
1406388
Hom.:
694011
Cov.:
23
AF XY:
0.994
AC XY:
699020
AN XY:
703480
show subpopulations
Gnomad4 AFR exome
AF:
0.754
AC:
24428
AN:
32404
Gnomad4 AMR exome
AF:
0.985
AC:
43980
AN:
44654
Gnomad4 ASJ exome
AF:
0.999
AC:
25759
AN:
25790
Gnomad4 EAS exome
AF:
1.00
AC:
39410
AN:
39410
Gnomad4 SAS exome
AF:
0.999
AC:
85084
AN:
85148
Gnomad4 FIN exome
AF:
1.00
AC:
53380
AN:
53380
Gnomad4 NFE exome
AF:
1.00
AC:
1060924
AN:
1061392
Gnomad4 Remaining exome
AF:
0.984
AC:
57600
AN:
58542
Heterozygous variant carriers
0
397
793
1190
1586
1983
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
20302
40604
60906
81208
101510
<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
AF:
0.930
AC:
141644
AN:
152244
Hom.:
66742
Cov.:
32
AF XY:
0.932
AC XY:
69376
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.759
AC:
0.758896
AN:
0.758896
Gnomad4 AMR
AF:
0.972
AC:
0.971518
AN:
0.971518
Gnomad4 ASJ
AF:
0.999
AC:
0.999136
AN:
0.999136
Gnomad4 EAS
AF:
1.00
AC:
0.999807
AN:
0.999807
Gnomad4 SAS
AF:
0.999
AC:
0.998964
AN:
0.998964
Gnomad4 FIN
AF:
1.00
AC:
1
AN:
1
Gnomad4 NFE
AF:
0.999
AC:
0.999133
AN:
0.999133
Gnomad4 OTH
AF:
0.957
AC:
0.957386
AN:
0.957386
Heterozygous variant carriers
0
409
819
1228
1638
2047
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
902
1804
2706
3608
4510
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.978
Hom.:
41239
Bravo
AF:
0.921
Asia WGS
AF:
0.984
AC:
3422
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:4
-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

Jun 11, 2014
Eurofins Ntd Llc (ga)
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

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

- -

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

- -

Propionic acidemia Benign:4
-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

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

- -

Jul 01, 2021
Pars Genome Lab
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Sep 05, 2021
Genome-Nilou Lab
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:3
Mar 03, 2015
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Feb 29, 2016
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.084
DANN
Benign
0.42
Mutation Taster
=100/0
polymorphism (auto)

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: rs4306370; hg19: chr13-100921056; API