chr13-100129838-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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: Myriad Women’s Health, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000282.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCCA	NM_000282.4	MANE Select	c.300+17777C>T		intron	N/A	NP_000273.2	P05165-1
	PCCA	NM_001352605.2		c.300+17777C>T		intron	N/A	NP_001339534.1
	PCCA	NM_001127692.3		c.222+17777C>T		intron	N/A	NP_001121164.1	P05165-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCCA	ENST00000376285.6	TSL:1 MANE Select	c.300+17777C>T		intron	N/A	ENSP00000365462.1	P05165-1
	PCCA	ENST00000881637.1		c.300+17777C>T		intron	N/A	ENSP00000551696.1
	PCCA	ENST00000881640.1		c.300+17777C>T		intron	N/A	ENSP00000551699.1

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

African (AFR) AF: 0.248 AC: 10297 AN: 41484

American (AMR) AF: 0.377 AC: 5767 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1851 AN: 3472

East Asian (EAS) AF: 0.298 AC: 1539 AN: 5172

South Asian (SAS) AF: 0.350 AC: 1688 AN: 4816

European-Finnish (FIN) AF: 0.467 AC: 4922 AN: 10548

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35564 AN: 67970

Other (OTH) AF: 0.462 AC: 975 AN: 2110

Alfa AF: 0.487 Hom.: 58339

Bravo AF: 0.405

Asia WGS AF: 0.329 AC: 1145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.50
PhyloP100		-1.7
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: rs1890139; hg19: chr13-100782092;