13-100089117-A-C

Variant names:

• chr13-100089117-A-C
• rs2046021682
• NM_000282.4:c.-4A>C

Variant summary

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

The NM_000282.4(PCCA):​c.-4A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000744 in 1,344,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: PCCA NM_000282.4 5_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.0900
• 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=-0.84).

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.-4A>C		5_prime_UTR	Exon 1 of 24	NP_000273.2	P05165-1
	PCCA	NM_001352605.2		c.-4A>C		5_prime_UTR	Exon 1 of 23	NP_001339534.1
	PCCA	NM_001127692.3		c.-4A>C		5_prime_UTR	Exon 1 of 23	NP_001121164.1	P05165-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCCA	ENST00000376285.6	TSL:1 MANE Select	c.-4A>C		5_prime_UTR	Exon 1 of 24	ENSP00000365462.1	P05165-1
	PCCA	ENST00000881637.1		c.-4A>C		5_prime_UTR	Exon 1 of 25	ENSP00000551696.1
	PCCA	ENST00000881640.1		c.-4A>C		5_prime_UTR	Exon 1 of 25	ENSP00000551699.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.44e-7 AC: 1 AN: 1344306 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 658572

African (AFR) AF: 0.00 AC: 0 AN: 28206

American (AMR) AF: 0.00 AC: 0 AN: 31530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23484

East Asian (EAS) AF: 0.00 AC: 0 AN: 31946

South Asian (SAS) AF: 0.00 AC: 0 AN: 71450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4992

European-Non Finnish (NFE) AF: 9.51e-7 AC: 1 AN: 1051344

Other (OTH) AF: 0.00 AC: 0 AN: 55464

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Propionic acidemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.7
DANN	Benign	0.68
PhyloP100		-0.090
PromoterAI		-0.33	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2046021682; hg19: chr13-100741371;