NM_000532.5:c.-34G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000532.5(PCCB):​c.-34G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: PCCB NM_000532.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• 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: G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Orphanet, ClinGen, Myriad Women’s Health

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.5
DANN	Benign	0.64
PhyloP100		-0.34
PromoterAI		0.29	Neutral

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;