rs144001285

Positions:

• chr3-136329857-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_000532.5(PCCB):​c.1499-48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,610,844 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (15 hom.)
• Consequence: PCCB NM_000532.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.908

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-136329857-A-G is Benign according to our data. Variant chr3-136329857-A-G is described in ClinVar as [Benign]. Clinvar id is 256373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCCB	NM_000532.5	c.1499-48A>G		intron_variant		ENST00000251654.9	NP_000523.2
PCCB	NM_001178014.2	c.1559-48A>G		intron_variant			NP_001171485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCCB	ENST00000251654.9	c.1499-48A>G		intron_variant		1	NM_000532.5	ENSP00000251654	P2

Frequencies

GnomAD3 genomes AF: 0.00232 AC: 353 AN: 152124 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00350

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00225 AC: 564 AN: 250130 Hom.: 1 AF XY: 0.00227 AC XY: 307 AN XY: 135254

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.00283

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000882

Gnomad FIN exome AF: 0.000463

Gnomad NFE exome AF: 0.00347

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00357 AC: 5210 AN: 1458602 Hom.: 15 Cov.: 30 AF XY: 0.00347 AC XY: 2521 AN XY: 725848

Gnomad4 AFR exome AF: 0.000748

Gnomad4 AMR exome AF: 0.00318

Gnomad4 ASJ exome AF: 0.000268

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000859

Gnomad4 FIN exome AF: 0.000356

Gnomad4 NFE exome AF: 0.00427

Gnomad4 OTH exome AF: 0.00345

GnomAD4 genome AF: 0.00232 AC: 353 AN: 152242 Hom.: 1 Cov.: 32 AF XY: 0.00222 AC XY: 165 AN XY: 74426

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.00445

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00350

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00256 Hom.: 0

Bravo AF: 0.00258

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.12
DANN	Benign	0.67

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: rs144001285; hg19: chr3-136048699;