rs9844666

Variant names:

• chr3-136255374-G-A
• rs9844666
• NM_000532.5:c.184-482G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 42 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: Myriad Women’s Health, ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000532.5. 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
	PCCB	NM_000532.5	MANE Select	c.184-482G>A		intron	N/A	NP_000523.2	P05166-1
	PCCB	NM_001178014.2		c.184-482G>A		intron	N/A	NP_001171485.1	P05166-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCCB	ENST00000251654.9	TSL:1 MANE Select	c.184-482G>A		intron	N/A	ENSP00000251654.4	P05166-1
	PCCB	ENST00000471595.5	TSL:1	c.184-482G>A		intron	N/A	ENSP00000417549.1	E9PDR0
	PCCB	ENST00000478469.5	TSL:1	c.184-482G>A		intron	N/A	ENSP00000420759.1	E7ENC1

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

African (AFR) AF: 0.0245 AC: 32 AN: 1304

American (AMR) AF: 0.120 AC: 419 AN: 3506

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 195 AN: 1054

East Asian (EAS) AF: 0.000357 AC: 1 AN: 2802

South Asian (SAS) AF: 0.245 AC: 1760 AN: 7184

European-Finnish (FIN) AF: 0.203 AC: 423 AN: 2082

Middle Eastern (MID) AF: 0.187 AC: 28 AN: 150

European-Non Finnish (NFE) AF: 0.219 AC: 7029 AN: 32166

Other (OTH) AF: 0.191 AC: 505 AN: 2646

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

African (AFR) AF: 0.0402 AC: 1672 AN: 41544

American (AMR) AF: 0.134 AC: 2053 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 792 AN: 3472

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5170

South Asian (SAS) AF: 0.229 AC: 1102 AN: 4810

European-Finnish (FIN) AF: 0.221 AC: 2339 AN: 10574

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16266 AN: 67948

Other (OTH) AF: 0.154 AC: 325 AN: 2110

Alfa AF: 0.213 Hom.: 17637

Bravo AF: 0.149

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.0
DANN	Benign	0.54
PhyloP100		0.99
PromoterAI		-0.026	Neutral
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: rs9844666; hg19: chr3-135974216;