13-100089061-C-A

Variant names:

• chr13-100089061-C-A
• rs778039561
• ENST00000376286.8:c.-60C>A

Variant summary

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

The ENST00000376286.8(PCCA):​c.-60C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000843 in 1,185,824 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: 8.4e-7 (0 hom.)
• Consequence: PCCA ENST00000376286.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.722
• 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]

PCCA-DT (HGNC:53266): (PCCA divergent transcript)

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=-0.57).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000376286.8. 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.-60C>A		upstream_gene	N/A	NP_000273.2	P05165-1
	PCCA	NM_001352605.2		c.-60C>A		upstream_gene	N/A	NP_001339534.1
	PCCA	NM_001127692.3		c.-60C>A		upstream_gene	N/A	NP_001121164.1	P05165-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCCA	ENST00000376286.8	TSL:2	c.-60C>A		5_prime_UTR	Exon 1 of 23	ENSP00000365463.4	P05165-2
	PCCA	ENST00000376279.7	TSL:2	c.-60C>A		5_prime_UTR	Exon 1 of 23	ENSP00000365456.3	P05165-3
	PCCA	ENST00000881624.1		c.-60C>A		5_prime_UTR	Exon 1 of 20	ENSP00000551683.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.43e-7 AC: 1 AN: 1185824 Hom.: 0 Cov.: 30 AF XY: 0.00000175 AC XY: 1 AN XY: 569860

⚠️ 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: 24064

American (AMR) AF: 0.00 AC: 0 AN: 12176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17018

East Asian (EAS) AF: 0.00 AC: 0 AN: 27478

South Asian (SAS) AF: 0.0000226 AC: 1 AN: 44252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4684

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 968264

Other (OTH) AF: 0.00 AC: 0 AN: 47882

⚠️ 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	-0.57
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		0.72
PromoterAI		0.11	Neutral

Splicing

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

Other links and lift over

dbSNP: rs778039561; hg19: chr13-100741315;