Variant chr13-100368441-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
PCCA	NM_000282.4 link	c.1644-31A>G		intron_variant		ENST00000376285.6	NP_000273.2	P05165-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCCA	ENST00000376285.6 link	c.1644-31A>G		intron_variant		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

GnomAD3 exomes

AF:

0.677

AC:

164516

AN:

242874

Hom.:

57163

AF XY:

0.681

AC XY:

89510

AN XY:

131460

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 SAS exome

AF:

0.568

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

Gnomad4 AFR exome

AF:

0.509

Gnomad4 AMR exome

AF:

0.618

Gnomad4 ASJ exome

AF:

0.714

Gnomad4 EAS exome

AF:

0.517

Gnomad4 SAS exome

AF:

0.575

Gnomad4 FIN exome

AF:

0.692

Gnomad4 NFE exome

AF:

0.782

Gnomad4 OTH exome

AF:

0.713

GnomAD4 genome

AF:

0.660

AC:

100254

AN:

151920

Hom.:

34172

Cov.:

AF XY:

0.653

AC XY:

48444

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.503

Gnomad4 AMR

AF:

0.660

Gnomad4 ASJ

AF:

0.708

Gnomad4 EAS

AF:

0.461

Gnomad4 SAS

AF:

0.544

Gnomad4 FIN

AF:

0.678

Gnomad4 NFE

AF:

0.770

Gnomad4 OTH

AF:

0.713

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 25, 2016	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Propionic acidemia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.69

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over