13-100089052-T-G

Position:

• chr13-100089052-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000376286.8(PCCA):​c.-69T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000629 in 1,323,318 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00032 (4 hom.)
• Consequence: PCCA ENST00000376286.8 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.675

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 13-100089052-T-G is Benign according to our data. Variant chr13-100089052-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1190369.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCCA	NM_000282.4			upstream_gene_variant		ENST00000376285.6	NP_000273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCCA	ENST00000376279.7	c.-69T>G		5_prime_UTR_variant	1/23	2		ENSP00000365456
PCCA	ENST00000376286.8	c.-69T>G		5_prime_UTR_variant	1/23	2		ENSP00000365463
PCCA	ENST00000376285.6			upstream_gene_variant		1	NM_000282.4	ENSP00000365462	P1
PCCA	ENST00000647303.1			upstream_gene_variant				ENSP00000495663

Frequencies

GnomAD3 genomes AF: 0.00302 AC: 460 AN: 152226 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00987

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000318 AC: 372 AN: 1170974 Hom.: 4 Cov.: 30 AF XY: 0.000274 AC XY: 154 AN XY: 561472

Gnomad4 AFR exome AF: 0.0119

Gnomad4 AMR exome AF: 0.00159

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000485

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000625

Gnomad4 OTH exome AF: 0.00123

GnomAD4 genome AF: 0.00302 AC: 460 AN: 152344 Hom.: 5 Cov.: 33 AF XY: 0.00281 AC XY: 209 AN XY: 74498

Gnomad4 AFR AF: 0.00986

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00284 Hom.: 1

Bravo AF: 0.00394

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.7
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs368695107; hg19: chr13-100741306;