3-136267245-A-G

Variant names:

• chr3-136267245-A-G
• rs606725
• NM_000532.5:c.543+5180A>G

Variant summary

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

The NM_000532.5(PCCB):​c.543+5180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,128 control chromosomes in the GnomAD database, including 42,940 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 0.75 (42940 hom., cov: 33)
• Consequence: PCCB NM_000532.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 3 publications found

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]

PCCB Gene-Disease associations (from GenCC):

• propionic acidemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Myriad Women’s Health, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCCB	NM_000532.5	c.543+5180A>G		intron_variant	Intron 5 of 14	ENST00000251654.9	NP_000523.2
PCCB	NM_001178014.2	c.603+5180A>G		intron_variant	Intron 6 of 15		NP_001171485.1
PCCB	XM_011512873.2	c.543+5180A>G		intron_variant	Intron 5 of 10		XP_011511175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCCB	ENST00000251654.9	c.543+5180A>G		intron_variant	Intron 5 of 14	1	NM_000532.5	ENSP00000251654.4

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113951 AN: 152008 Hom.: 42904 Cov.: 33

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.750 AC: 114042 AN: 152128 Hom.: 42940 Cov.: 33 AF XY: 0.755 AC XY: 56127 AN XY: 74348

African (AFR) AF: 0.691 AC: 28676 AN: 41494

American (AMR) AF: 0.755 AC: 11543 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2341 AN: 3468

East Asian (EAS) AF: 0.863 AC: 4461 AN: 5172

South Asian (SAS) AF: 0.810 AC: 3902 AN: 4820

European-Finnish (FIN) AF: 0.860 AC: 9110 AN: 10588

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51693 AN: 67986

Other (OTH) AF: 0.724 AC: 1522 AN: 2102

Alfa AF: 0.756 Hom.: 5448

Bravo AF: 0.738

Asia WGS AF: 0.834 AC: 2900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.71
DANN	Benign	0.39
PhyloP100		-2.1
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: rs606725; hg19: chr3-135986087;