13-100089138-C-T

Variant names:

• chr13-100089138-C-T
• rs752423629
• NM_000282.4:c.18C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001352610.2(PCCA):​c.-849C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,356,526 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: PCCA NM_001352610.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -2.71
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 13-100089138-C-T is Benign according to our data. Variant chr13-100089138-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1102071.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352610.2. 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.18C>T	p.Val6Val	synonymous	Exon 1 of 24	NP_000273.2	P05165-1
	PCCA	NM_001352610.2		c.-849C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 23	NP_001339539.1
	PCCA	NM_001352611.2		c.-849C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 22	NP_001339540.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCCA	ENST00000376285.6	TSL:1 MANE Select	c.18C>T	p.Val6Val	synonymous	Exon 1 of 24	ENSP00000365462.1	P05165-1
	PCCA	ENST00000881637.1		c.18C>T	p.Val6Val	synonymous	Exon 1 of 25	ENSP00000551696.1
	PCCA	ENST00000881640.1		c.18C>T	p.Val6Val	synonymous	Exon 1 of 25	ENSP00000551699.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000760 AC: 1 AN: 131512 AF XY: 0.0000140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000116

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1356526 Hom.: 0 Cov.: 31 AF XY: 0.00000150 AC XY: 1 AN XY: 666556

African (AFR) AF: 0.00 AC: 0 AN: 28606

American (AMR) AF: 0.00 AC: 0 AN: 33024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23702

East Asian (EAS) AF: 0.00 AC: 0 AN: 32650

South Asian (SAS) AF: 0.00 AC: 0 AN: 73110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4664

European-Non Finnish (NFE) AF: 9.44e-7 AC: 1 AN: 1059496

Other (OTH) AF: 0.00 AC: 0 AN: 56102

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	2	Propionic acidemia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.98
DANN	Benign	0.86
PhyloP100		-2.7
PromoterAI		0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs752423629; hg19: chr13-100741392;