chr13-100246275-A-C

Variant names:

• chr13-100246275-A-C
• rs681561
• NM_000282.4:c.637+10397A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000282.4(PCCA):​c.637+10397A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 150,566 control chromosomes in the GnomAD database, including 23,612 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (23612 hom., cov: 32)
• Consequence: PCCA NM_000282.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688
• Publications: 8 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCCA	NM_000282.4	c.637+10397A>C		intron_variant	Intron 8 of 23	ENST00000376285.6	NP_000273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCCA	ENST00000376285.6	c.637+10397A>C		intron_variant	Intron 8 of 23	1	NM_000282.4	ENSP00000365462.1

Frequencies

GnomAD3 genomes AF: 0.557 AC: 83770 AN: 150448 Hom.: 23581 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.523

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.557 AC: 83842 AN: 150566 Hom.: 23612 Cov.: 32 AF XY: 0.560 AC XY: 41255 AN XY: 73624

African (AFR) AF: 0.636 AC: 26181 AN: 41146

American (AMR) AF: 0.572 AC: 8660 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1631 AN: 3460

East Asian (EAS) AF: 0.760 AC: 3934 AN: 5178

South Asian (SAS) AF: 0.704 AC: 3370 AN: 4790

European-Finnish (FIN) AF: 0.505 AC: 5275 AN: 10448

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.493 AC: 33119 AN: 67112

Other (OTH) AF: 0.525 AC: 1103 AN: 2100

Alfa AF: 0.491 Hom.: 22961

Bravo AF: 0.557

Asia WGS AF: 0.731 AC: 2538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.67
DANN	Benign	0.73
PhyloP100		-0.69
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

Other links and lift over

dbSNP: rs681561; hg19: chr13-100898529;