rs35820208

chr8-93903875-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000523021.1(PDP1):n.389-17352G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 149,230 control chromosomes in the GnomAD database, including 340 homozygotes. 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: 𝑓 0.062 (340 hom., cov: 29)
• Consequence: PDP1 ENST00000523021.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

Genes affected

PDP1 (HGNC:9279): (pyruvate dehydrogenase phosphatase catalytic subunit 1) Pyruvate dehydrogenase (E1) is one of the three components (E1, E2, and E3) of the large pyruvate dehydrogenase complex. Pyruvate dehydrogenase kinases catalyze phosphorylation of serine residues of E1 to inactivate the E1 component and inhibit the complex. Pyruvate dehydrogenase phosphatases catalyze the dephosphorylation and activation of the E1 component to reverse the effects of pyruvate dehydrogenase kinases. Pyruvate dehydrogenase phosphatase is a heterodimer consisting of catalytic and regulatory subunits. Two catalytic subunits have been reported; one is predominantly expressed in skeletal muscle and another one is is much more abundant in the liver. The catalytic subunit, encoded by this gene, is the former, and belongs to the protein phosphatase 2C (PP2C) superfamily. Along with the pyruvate dehydrogenase complex and pyruvate dehydrogenase kinases, this enzyme is located in the mitochondrial matrix. Mutation in this gene causes pyruvate dehydrogenase phosphatase deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDP1	ENST00000523021.1	n.389-17352G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 9196 AN: 149156 Hom.: 341 Cov.: 29

Gnomad AFR AF: 0.0441

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000395

Gnomad SAS AF: 0.0541

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.113

Gnomad NFE AF: 0.0723

Gnomad OTH AF: 0.0775

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

GnomAD4 genome AF: 0.0616 AC: 9192 AN: 149230 Hom.: 340 Cov.: 29 AF XY: 0.0610 AC XY: 4429 AN XY: 72614

Gnomad4 AFR AF: 0.0440

Gnomad4 AMR AF: 0.0613

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.000396

Gnomad4 SAS AF: 0.0543

Gnomad4 FIN AF: 0.0623

Gnomad4 NFE AF: 0.0722

Gnomad4 OTH AF: 0.0768

Alfa AF: 0.0640 Hom.: 45

Bravo AF: 0.0614

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.46
Dann	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35820208; hg19: chr8-94916103;