13-100530356-C-A

Variant names:

• chr13-100530356-C-A
• rs41281124
• NM_000282.4:c.*190C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000282.4(PCCA):​c.*190C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000203 in 493,050 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: PCCA NM_000282.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54
• Publications: 0 publications found

Genes affected

PCCA (HGNC:8653): (propionyl-CoA carboxylase subunit alpha) The protein encoded by this gene is the alpha subunit of the heterodimeric mitochondrial enzyme Propionyl-CoA carboxylase. PCCA encodes the biotin-binding region of this enzyme. Mutations in either PCCA or PCCB (encoding the beta subunit) lead to an enzyme deficiency resulting in propionic acidemia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

GGACT (HGNC:25100): (gamma-glutamylamine cyclotransferase) The protein encoded by this gene aids in the proteolytic degradation of crosslinked fibrin by breaking down isodipeptide L-gamma-glutamyl-L-epsilon-lysine, a byproduct of fibrin degradation. The reaction catalyzed by the encoded gamma-glutamylaminecyclotransferase produces 5-oxo-L-proline and a free alkylamine. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Aug 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.12).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000282.4. 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
	PCCA	NM_000282.4	MANE Select	c.*190C>A		3_prime_UTR	Exon 24 of 24	NP_000273.2	P05165-1
	GGACT	NM_001195087.2	MANE Select	c.*1774G>T		3_prime_UTR	Exon 3 of 3	NP_001182016.1	Q9BVM4
	PCCA	NM_001352605.2		c.*190C>A		3_prime_UTR	Exon 23 of 23	NP_001339534.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCCA	ENST00000376285.6	TSL:1 MANE Select	c.*190C>A		3_prime_UTR	Exon 24 of 24	ENSP00000365462.1	P05165-1
	GGACT	ENST00000683975.1	MANE Select	c.*1774G>T		3_prime_UTR	Exon 3 of 3	ENSP00000508020.1	Q9BVM4
	GGACT	ENST00000455100.2	TSL:1	c.*1774G>T		3_prime_UTR	Exon 2 of 2	ENSP00000410449.1	Q9BVM4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000203 AC: 1 AN: 493050 Hom.: 0 Cov.: 4 AF XY: 0.00000381 AC XY: 1 AN XY: 262444

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 14124

American (AMR) AF: 0.00 AC: 0 AN: 28876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16280

East Asian (EAS) AF: 0.00 AC: 0 AN: 31360

South Asian (SAS) AF: 0.00 AC: 0 AN: 50886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2522

European-Non Finnish (NFE) AF: 0.00000347 AC: 1 AN: 288306

Other (OTH) AF: 0.00 AC: 0 AN: 27862

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.12
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		2.5

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: rs41281124; hg19: chr13-101182610;