rs144001285

Variant names:

• chr3-136329857-A-G
• rs144001285
• NM_000532.5:c.1499-48A>G

Variant summary

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 256373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 15 AR gene

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.1499-48A>G		intron	N/A	NP_000523.2
	PCCB	NM_001178014.2		c.1559-48A>G		intron	N/A	NP_001171485.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCCB	ENST00000251654.9	TSL:1 MANE Select	c.1499-48A>G		intron	N/A	ENSP00000251654.4
	PCCB	ENST00000471595.5	TSL:1	c.1499-48A>G		intron	N/A	ENSP00000417549.1
	PCCB	ENST00000478469.5	TSL:1	c.885-4423A>G		intron	N/A	ENSP00000420759.1

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

GnomAD2 exomes AF: 0.00225 AC: 564 AN: 250130 AF XY: 0.00227

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 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

African (AFR) AF: 0.000748 AC: 25 AN: 33408

American (AMR) AF: 0.00318 AC: 142 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.000859 AC: 74 AN: 86164

European-Finnish (FIN) AF: 0.000356 AC: 19 AN: 53330

Middle Eastern (MID) AF: 0.000524 AC: 3 AN: 5724

European-Non Finnish (NFE) AF: 0.00427 AC: 4732 AN: 1109310

Other (OTH) AF: 0.00345 AC: 208 AN: 60220

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

African (AFR) AF: 0.000698 AC: 29 AN: 41548

American (AMR) AF: 0.00445 AC: 68 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00350 AC: 238 AN: 68016

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00256 Hom.: 0

Bravo AF: 0.00258

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.12
DANN	Benign	0.67
PhyloP100		-0.91
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs144001285; hg19: chr3-136048699;