rs9844666

chr3-136255374-G-A

Variant summary

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

The NM_000532.5(PCCB):c.184-482G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 205,002 control chromosomes in the GnomAD database, including 3,966 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 0.16 (2682 hom., cov: 32)
  • Exomes 𝑓: 0.20 (1284 hom.)
• Consequence: PCCB NM_000532.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.995

Genes affected

PCCB (HGNC:8654): (propionyl-CoA carboxylase subunit beta) The protein encoded by this gene is a subunit of the propionyl-CoA carboxylase (PCC) enzyme, which is involved in the catabolism of propionyl-CoA. PCC is a mitochondrial enzyme that probably acts as a dodecamer of six alpha subunits and six beta subunits. This gene encodes the beta subunit of PCC. Defects in this gene are a cause of propionic acidemia type II (PA-2). 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCCB	NM_000532.5	c.184-482G>A		intron_variant		ENST00000251654.9
PCCB	NM_001178014.2	c.184-482G>A		intron_variant
PCCB	XM_011512873.2	c.184-482G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCCB	ENST00000251654.9	c.184-482G>A		intron_variant		1	NM_000532.5	P2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24786 AN: 151990 Hom.: 2683 Cov.: 32

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.196 AC: 10392 AN: 52894 Hom.: 1284 Cov.: 0 AF XY: 0.201 AC XY: 5651 AN XY: 28110

Gnomad4 AFR exome AF: 0.0245

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.000357

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.203

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.163 AC: 24772 AN: 152108 Hom.: 2682 Cov.: 32 AF XY: 0.162 AC XY: 12056 AN XY: 74342

Gnomad4 AFR AF: 0.0402

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.154

Alfa AF: 0.224 Hom.: 9120

Bravo AF: 0.149

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	9.0
Dann	Benign	0.54

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: rs9844666; hg19: chr3-135974216;