rs1556800

Positions:

• chr13-100157551-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000282.4(PCCA):​c.468+211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,254 control chromosomes in the GnomAD database, including 1,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1659 hom., cov: 33)
• Consequence: PCCA NM_000282.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.176

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 13-100157551-A-G is Benign according to our data. Variant chr13-100157551-A-G is described in ClinVar as [Benign]. Clinvar id is 669947.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCCA	NM_000282.4	c.468+211A>G		intron_variant		ENST00000376285.6	NP_000273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCCA	ENST00000376285.6	c.468+211A>G		intron_variant		1	NM_000282.4	ENSP00000365462.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21630 AN: 152136 Hom.: 1654 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.0896

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.0574

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.138

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.142 AC: 21645 AN: 152254 Hom.: 1659 Cov.: 33 AF XY: 0.139 AC XY: 10371 AN XY: 74434

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0897

Gnomad4 ASJ AF: 0.0746

Gnomad4 EAS AF: 0.0575

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.143

Alfa AF: 0.141 Hom.: 278

Bravo AF: 0.136

Asia WGS AF: 0.141 AC: 493 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs1556800; hg19: chr13-100809805;