rs372649775

Variant names:

• chr3-136250342-G-A
• rs372649775
• NM_000532.5:c.-34G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-136250342-G-A
• chr3-136250342-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000532.5(PCCB):​c.-34G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000412 in 1,483,054 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00068 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00038 (1 hom.)
• Consequence: PCCB NM_000532.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.337
• 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: Myriad Women’s Health, ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

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.-34G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_000523.2	P05166-1
	PCCB	NM_000532.5	MANE Select	c.-34G>A		5_prime_UTR	Exon 1 of 15	NP_000523.2	P05166-1
	PCCB	NM_001178014.2		c.-34G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	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.-34G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	ENSP00000251654.4	P05166-1
	PCCB	ENST00000251654.9	TSL:1 MANE Select	c.-34G>A		5_prime_UTR	Exon 1 of 15	ENSP00000251654.4	P05166-1
	PCCB	ENST00000878348.1		c.-34G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	ENSP00000548407.1

Frequencies

GnomAD3 genomes AF: 0.000677 AC: 103 AN: 152240 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00602

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000852 AC: 87 AN: 102146 AF XY: 0.000660

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000560

Gnomad ASJ exome AF: 0.00138

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00528

Gnomad NFE exome AF: 0.000570

Gnomad OTH exome AF: 0.000353

GnomAD4 exome AF: 0.000382 AC: 508 AN: 1330814 Hom.: 1 Cov.: 31 AF XY: 0.000344 AC XY: 223 AN XY: 648482

African (AFR) AF: 0.0000336 AC: 1 AN: 29758

American (AMR) AF: 0.000106 AC: 3 AN: 28344

Ashkenazi Jewish (ASJ) AF: 0.00179 AC: 37 AN: 20662

East Asian (EAS) AF: 0.00 AC: 0 AN: 35084

South Asian (SAS) AF: 0.0000145 AC: 1 AN: 68874

European-Finnish (FIN) AF: 0.00504 AC: 227 AN: 45024

Middle Eastern (MID) AF: 0.000224 AC: 1 AN: 4460

European-Non Finnish (NFE) AF: 0.000205 AC: 214 AN: 1043744

Other (OTH) AF: 0.000437 AC: 24 AN: 54864

GnomAD4 genome AF: 0.000677 AC: 103 AN: 152240 Hom.: 1 Cov.: 33 AF XY: 0.000888 AC XY: 66 AN XY: 74366

African (AFR) AF: 0.0000241 AC: 1 AN: 41480

American (AMR) AF: 0.000196 AC: 3 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00602 AC: 64 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68040

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Propionic acidemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.7
DANN	Benign	0.85
PhyloP100		-0.34
PromoterAI		0.20	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs372649775; hg19: chr3-135969184;