rs886038276

Positions:

• chr13-100111929-ATTAT-A
• chr13-100111929-A-ATTAT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000282.4(PCCA):​c.231+47_231+50del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0951 in 1,586,396 control chromosomes in the GnomAD database, including 7,910 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (687 hom., cov: 30)
  • Exomes 𝑓: 0.095 (7223 hom.)
• Consequence: PCCA NM_000282.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.24

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 13-100111929-ATTAT-A is Benign according to our data. Variant chr13-100111929-ATTAT-A is described in ClinVar as [Benign]. Clinvar id is 255735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-100111929-ATTAT-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCCA	NM_000282.4	c.231+47_231+50del		intron_variant		ENST00000376285.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCCA	ENST00000376285.6	c.231+47_231+50del		intron_variant		1	NM_000282.4	P1

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14123 AN: 152030 Hom.: 684 Cov.: 30

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0868

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.102

GnomAD3 exomes AF: 0.0856 AC: 21325 AN: 249048 Hom.: 1041 AF XY: 0.0891 AC XY: 12029 AN XY: 134952

Gnomad AFR exome AF: 0.0963

Gnomad AMR exome AF: 0.0602

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.000437

Gnomad SAS exome AF: 0.115

Gnomad FIN exome AF: 0.0570

Gnomad NFE exome AF: 0.0992

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0953 AC: 136698 AN: 1434248 Hom.: 7223 AF XY: 0.0958 AC XY: 68548 AN XY: 715184

Gnomad4 AFR exome AF: 0.0980

Gnomad4 AMR exome AF: 0.0635

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.000558

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.0581

Gnomad4 NFE exome AF: 0.0994

Gnomad4 OTH exome AF: 0.0978

GnomAD4 genome AF: 0.0929 AC: 14134 AN: 152148 Hom.: 687 Cov.: 30 AF XY: 0.0913 AC XY: 6796 AN XY: 74408

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0868

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0588

Gnomad4 NFE AF: 0.0994

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0962 Hom.: 67

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Propionic acidemia Benign:4

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 18, 2023	- -
Benign, criteria provided, single submitter	research	Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital	Jan 01, 2011	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 25, 2019	- -

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)	Nov 15, 2012	- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs147037340; hg19: chr13-100764183;