rs180982841

Variant names:

• chr3-136293874-C-G
• rs180982841
• NM_000532.5:c.763+10C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-136293874-C-G
• chr3-136293874-C-A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_000532.5(PCCB):​c.763+10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000377 in 1,457,310 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (1 hom.)
• Consequence: PCCB NM_000532.5 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:2
• Conservation: PhyloP100: 0.0910
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine, Myriad Women's Health, ClinGen, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-136293874-C-G is Benign according to our data. Variant chr3-136293874-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 523374.

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.763+10C>G		intron	N/A	NP_000523.2	P05166-1
	PCCB	NM_001178014.2		c.823+10C>G		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.763+10C>G		intron	N/A	ENSP00000251654.4	P05166-1
	PCCB	ENST00000471595.5	TSL:1	c.763+10C>G		intron	N/A	ENSP00000417549.1	E9PDR0
	PCCB	ENST00000478469.5	TSL:1	c.763+10C>G		intron	N/A	ENSP00000420759.1	E7ENC1

Frequencies

GnomAD3 genomes AF: 0.000493 AC: 75 AN: 152096 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000458 AC: 115 AN: 250998 AF XY: 0.000472

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00386

Gnomad NFE exome AF: 0.000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000363 AC: 474 AN: 1305096 Hom.: 1 Cov.: 20 AF XY: 0.000368 AC XY: 242 AN XY: 657786

African (AFR) AF: 0.0000983 AC: 3 AN: 30506

American (AMR) AF: 0.0000224 AC: 1 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25192

East Asian (EAS) AF: 0.00 AC: 0 AN: 38996

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 82996

European-Finnish (FIN) AF: 0.00389 AC: 207 AN: 53216

Middle Eastern (MID) AF: 0.000732 AC: 4 AN: 5464

European-Non Finnish (NFE) AF: 0.000260 AC: 252 AN: 968962

Other (OTH) AF: 0.000109 AC: 6 AN: 55214

GnomAD4 genome AF: 0.000493 AC: 75 AN: 152214 Hom.: 0 Cov.: 32 AF XY: 0.000631 AC XY: 47 AN XY: 74434

African (AFR) AF: 0.0000722 AC: 3 AN: 41526

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00471 AC: 50 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000430 Hom.: 0

Bravo AF: 0.000136

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	2	1	Propionic acidemia (3)
-	1	-	Global developmental delay;C5574662:Hyperammonemia (1)
-	-	1	PCCB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.59
PhyloP100		0.091
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs180982841;

hg19: chr3-136012716;