Variant 8-93916851-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000523021.1(PDP1):n.389-4376T>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 0.433 in 237,796 control chromosomes in the GnomAD database, including 22,896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 14753 hom., cov: 30)

Exomes 𝑓: 0.43 ( 8143 hom. )

Consequence

PDP1
ENST00000523021.1 intron, non_coding_transcript

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.194

Variant links:

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]

PDP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 8-93916851-T-A is Benign according to our data. Variant chr8-93916851-T-A is described in ClinVar as [Benign]. Clinvar id is 369617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDP1	ENST00000523021.1 linkuse as main transcript	n.389-4376T>A		intron_variant, non_coding_transcript_variant		4
PDP1	ENST00000520614.1 linkuse as main transcript			upstream_gene_variant		4		ENSP00000430931

Frequencies

GnomAD3 genomes

AF:

0.436

AC:

65961

AN:

151388

Hom.:

14740

Cov.:

show subpopulations

Gnomad AFR

AF:

0.400

Gnomad AMI

AF:

0.411

Gnomad AMR

AF:

0.559

Gnomad ASJ

AF:

0.490

Gnomad EAS

AF:

0.673

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.428

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.406

Gnomad OTH

AF:

0.466

GnomAD4 exome

AF:

0.428

AC:

36918

AN:

86298

Hom.:

8143

Cov.:

AF XY:

0.435

AC XY:

21854

AN XY:

50248

show subpopulations

Gnomad4 AFR exome

AF:

0.411

Gnomad4 AMR exome

AF:

0.556

Gnomad4 ASJ exome

AF:

0.493

Gnomad4 EAS exome

AF:

0.629

Gnomad4 SAS exome

AF:

0.472

Gnomad4 FIN exome

AF:

0.420

Gnomad4 NFE exome

AF:

0.402

Gnomad4 OTH exome

AF:

0.434

GnomAD4 genome

AF:

0.436

AC:

66004

AN:

151498

Hom.:

14753

Cov.:

AF XY:

0.441

AC XY:

32654

AN XY:

74006

show subpopulations

Gnomad4 AFR

AF:

0.400

Gnomad4 AMR

AF:

0.559

Gnomad4 ASJ

AF:

0.490

Gnomad4 EAS

AF:

0.673

Gnomad4 SAS

AF:

0.485

Gnomad4 FIN

AF:

0.428

Gnomad4 NFE

AF:

0.406

Gnomad4 OTH

AF:

0.472

Alfa

AF:

0.258

Hom.:

579

Bravo

AF:

0.447

Asia WGS

AF:

0.576

AC:

1997

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Pyruvate dehydrogenase phosphatase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.59

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over