rs777359703

Variant names:

• chr3-136250376-ATGGCGGCGGCATTACGGG-A
• rs777359703
• NM_000532.5:c.11_28delCATTACGGGTGGCGGCGG

Your query was ambiguous. Multiple possible variants found:

• chr3-136250376-ATGGCGGCGGCATTACGGG-A
• chr3-136250376-ATGGCGGCGGCATTACGGG-ATGGCGGCGGCATTACGGGTGGCGGCGGCATTACGGG
• chr3-136250376-ATGGCGGCGGCATTACGGG-ATGGCGGCGGCATTACGGGTGGCGGCGGCATTACGGGTGGCGGCGGCATTACGGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_000532.5(PCCB):​c.11_28delCATTACGGGTGGCGGCGG​(p.Ala4_Ala9del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A4A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PCCB NM_000532.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.89
• 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: Uncertain_significance. The variant received 2 ACMG points.

• 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.11_28delCATTACGGGTGGCGGCGG	p.Ala4_Ala9del	disruptive_inframe_deletion	Exon 1 of 15	ENST00000251654.9	NP_000523.2
PCCB	NM_001178014.2	c.11_28delCATTACGGGTGGCGGCGG	p.Ala4_Ala9del	disruptive_inframe_deletion	Exon 1 of 16		NP_001171485.1
PCCB	XM_011512873.2	c.11_28delCATTACGGGTGGCGGCGG	p.Ala4_Ala9del	disruptive_inframe_deletion	Exon 1 of 11		XP_011511175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCCB	ENST00000251654.9	c.11_28delCATTACGGGTGGCGGCGG	p.Ala4_Ala9del	disruptive_inframe_deletion	Exon 1 of 15	1	NM_000532.5	ENSP00000251654.4

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.9
Mutation Taster		=27/173	disease causing (long InDel)

Splicing

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

Other links and lift over

dbSNP: rs777359703; hg19: chr3-135969218;