rs1890139

Variant names:

• chr13-100129838-C-T
• rs1890139
• NM_000282.4:c.300+17777C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000282.4(PCCA):​c.300+17777C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,048 control chromosomes in the GnomAD database, including 14,297 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 0.42 (14297 hom., cov: 32)
• Consequence: PCCA NM_000282.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCCA	NM_000282.4	c.300+17777C>T		intron_variant	Intron 4 of 23	ENST00000376285.6	NP_000273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCCA	ENST00000376285.6	c.300+17777C>T		intron_variant	Intron 4 of 23	1	NM_000282.4	ENSP00000365462.1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63276 AN: 151930 Hom.: 14290 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.416 AC: 63298 AN: 152048 Hom.: 14297 Cov.: 32 AF XY: 0.412 AC XY: 30612 AN XY: 74316

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.462

Alfa AF: 0.507 Hom.: 40427

Bravo AF: 0.405

Asia WGS AF: 0.329 AC: 1145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.50

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: rs1890139; hg19: chr13-100782092;