chr13-100368441-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.1644-31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 1,162,430 control chromosomes in the GnomAD database, including 311,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 34172 hom., cov: 31)

Exomes 𝑓: 0.73 ( 276942 hom. )

Consequence

PCCA
NM_000282.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.28

Publications

8 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=-0.8).

BP6

Variant 13-100368441-A-G is Benign according to our data. Variant chr13-100368441-A-G is described in ClinVar as Benign. ClinVar VariationId is 255734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCCA	NM_000282.4 link	c.1644-31A>G		intron_variant	Intron 18 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.1644-31A>G		intron_variant	Intron 18 of 23	1	NM_000282.4	ENSP00000365462.1		P05165-1

Frequencies

GnomAD3 genomes

AF:

0.660

AC:

100222

AN:

151802

Hom.:

34171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.504

Gnomad AMI

AF:

0.742

Gnomad AMR

AF:

0.662

Gnomad ASJ

AF:

0.708

Gnomad EAS

AF:

0.461

Gnomad SAS

AF:

0.543

Gnomad FIN

AF:

0.678

Gnomad MID

AF:

0.797

Gnomad NFE

AF:

0.770

Gnomad OTH

AF:

0.709

GnomAD2 exomes

AF:

0.677

AC:

164516

AN:

242874

AF XY:

0.681

show subpopulations

Gnomad AFR exome

AF:

0.506

Gnomad AMR exome

AF:

0.615

Gnomad ASJ exome

AF:

0.716

Gnomad EAS exome

AF:

0.462

Gnomad FIN exome

AF:

0.682

Gnomad NFE exome

AF:

0.776

Gnomad OTH exome

AF:

0.721

GnomAD4 exome

AF:

0.734

AC:

742152

AN:

1010510

Hom.:

276942

Cov.:

AF XY:

0.729

AC XY:

381294

AN XY:

522740

show subpopulations

African (AFR)

AF:

0.509

AC:

12184

AN:

23960

American (AMR)

AF:

0.618

AC:

26704

AN:

43210

Ashkenazi Jewish (ASJ)

AF:

0.714

AC:

16539

AN:

23162

East Asian (EAS)

AF:

0.517

AC:

19052

AN:

36864

South Asian (SAS)

AF:

0.575

AC:

42781

AN:

74418

European-Finnish (FIN)

AF:

0.692

AC:

36653

AN:

52952

Middle Eastern (MID)

AF:

0.764

AC:

3717

AN:

4862

European-Non Finnish (NFE)

AF:

0.782

AC:

552459

AN:

706112

Other (OTH)

AF:

0.713

AC:

32063

AN:

44970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

9454

18908

28362

37816

47270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10202

20404

30606

40808

51010

<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:

0.660

AC:

100254

AN:

151920

Hom.:

34172

Cov.:

AF XY:

0.653

AC XY:

48444

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.503

AC:

20837

AN:

41420

American (AMR)

AF:

0.660

AC:

10076

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.708

AC:

2456

AN:

3470

East Asian (EAS)

AF:

0.461

AC:

2377

AN:

5158

South Asian (SAS)

AF:

0.544

AC:

2614

AN:

4804

European-Finnish (FIN)

AF:

0.678

AC:

7148

AN:

10540

Middle Eastern (MID)

AF:

0.799

AC:

235

AN:

294

European-Non Finnish (NFE)

AF:

0.770

AC:

52331

AN:

67958

Other (OTH)

AF:

0.713

AC:

1503

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1656

3312

4968

6624

8280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<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:

0.692

Hom.:

4811

Bravo

AF:

0.655

Asia WGS

AF:

0.482

AC:

1672

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 25, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

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

- -

Propionic acidemia

Benign:2

Sep 05, 2021

Genome-Nilou Lab

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

2.3

PromoterAI

-0.0084

Neutral

(source)

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