13-100268802-A-G

Variant names:

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

Clinical Significance

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

Conservation

PhyloP100: -0.760

Publications

7 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

PCCA links:

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 VariationId is 92765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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
PCCA	NM_000282.4 link	c.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
PCCA	ENST00000376285.6 link	c.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.:

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.:

AF XY:

0.994

AC XY:

699020

AN XY:

703480

show subpopulations

African (AFR)

AF:

0.754

AC:

24428

AN:

32404

American (AMR)

AF:

0.985

AC:

43980

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.999

AC:

25759

AN:

25790

East Asian (EAS)

AF:

1.00

AC:

39410

AN:

39410

South Asian (SAS)

AF:

0.999

AC:

85084

AN:

85148

European-Finnish (FIN)

AF:

1.00

AC:

53380

AN:

53380

Middle Eastern (MID)

AF:

0.987

AC:

5596

AN:

5668

European-Non Finnish (NFE)

AF:

1.00

AC:

1060924

AN:

1061392

Other (OTH)

AF:

0.984

AC:

57600

AN:

58542

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

397

793

1190

1586

1983

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

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.:

AF XY:

0.932

AC XY:

69376

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.759

AC:

31479

AN:

41480

American (AMR)

AF:

0.972

AC:

14872

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.999

AC:

3469

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5179

AN:

5180

South Asian (SAS)

AF:

0.999

AC:

4821

AN:

4826

European-Finnish (FIN)

AF:

1.00

AC:

10624

AN:

10624

Middle Eastern (MID)

AF:

0.983

AC:

289

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67977

AN:

68036

Other (OTH)

AF:

0.957

AC:

2022

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

409

819

1228

1638

2047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

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

Clinical Genetics, Academic Medical Center

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

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Propionic acidemia

Benign:4

Jul 01, 2021

Pars Genome Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

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

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.084

(source)

DANN

Benign

0.42

PhyloP100

-0.76

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over