3-136250376-ATGGCGGCGGCATTACGGG-ATGGCGGCGGCATTACGGGTGGCGGCGGCATTACGGGTGGCGGCGGCATTACGGG

Variant names:

• chr3-136250376-A-ATGGCGGCGGCATTACGGGTGGCGGCGGCATTACGGG
• NM_000532.5:c.28_29insCATTACGGGTGGCGGCGGCATTACGGGTGGCGGCGG

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_000532.5(PCCB):​c.28_29insCATTACGGGTGGCGGCGGCATTACGGGTGGCGGCGG​(p.Ala9_Val10insAlaLeuArgValAlaAlaAlaLeuArgValAlaAla) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,373,862 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: PCCB NM_000532.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.47

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000532.5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCCB	NM_000532.5	c.28_29insCATTACGGGTGGCGGCGGCATTACGGGTGGCGGCGG	p.Ala9_Val10insAlaLeuArgValAlaAlaAlaLeuArgValAlaAla	disruptive_inframe_insertion	Exon 1 of 15	ENST00000251654.9	NP_000523.2
PCCB	NM_001178014.2	c.28_29insCATTACGGGTGGCGGCGGCATTACGGGTGGCGGCGG	p.Ala9_Val10insAlaLeuArgValAlaAlaAlaLeuArgValAlaAla	disruptive_inframe_insertion	Exon 1 of 16		NP_001171485.1
PCCB	XM_011512873.2	c.28_29insCATTACGGGTGGCGGCGGCATTACGGGTGGCGGCGG	p.Ala9_Val10insAlaLeuArgValAlaAlaAlaLeuArgValAlaAla	disruptive_inframe_insertion	Exon 1 of 11		XP_011511175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCCB	ENST00000251654.9	c.28_29insCATTACGGGTGGCGGCGGCATTACGGGTGGCGGCGG	p.Ala9_Val10insAlaLeuArgValAlaAlaAlaLeuArgValAlaAla	disruptive_inframe_insertion	Exon 1 of 15	1	NM_000532.5	ENSP00000251654.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1373862 Hom.: 0 Cov.: 31 AF XY: 0.00000297 AC XY: 2 AN XY: 674084

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000548

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-135969218;