rs2184971

Variant names:

• chr13-100165838-A-G
• rs2184971
• NM_000282.4:c.468+8498A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-100165838-A-G
• chr13-100165838-A-T

Variant summary

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

The NM_000282.4(PCCA):​c.468+8498A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,874 control chromosomes in the GnomAD database, including 19,280 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 0.50 (19280 hom., cov: 31)
• Consequence: PCCA NM_000282.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCCA	NM_000282.4	c.468+8498A>G		intron_variant	Intron 6 of 23	ENST00000376285.6	NP_000273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCCA	ENST00000376285.6	c.468+8498A>G		intron_variant	Intron 6 of 23	1	NM_000282.4	ENSP00000365462.1

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75137 AN: 151756 Hom.: 19248 Cov.: 31

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.495 AC: 75222 AN: 151874 Hom.: 19280 Cov.: 31 AF XY: 0.503 AC XY: 37329 AN XY: 74212

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.447

Alfa AF: 0.461 Hom.: 2556

Bravo AF: 0.494

Asia WGS AF: 0.720 AC: 2502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.56
DANN	Benign	0.33

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: rs2184971; hg19: chr13-100818092;