Variant 8-93917734-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_018444.4(PDP1):c.-45+655C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00807 in 1,349,458 control chromosomes in the GnomAD database, including 388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 174 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 214 hom. )

Consequence

PDP1
NM_018444.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.814

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 8-93917734-C-T is Benign according to our data. Variant chr8-93917734-C-T is described in ClinVar as [Benign]. Clinvar id is 1221977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDP1	NM_018444.4 linkuse as main transcript	c.-45+655C>T		intron_variant		ENST00000297598.5	NP_060914.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDP1	ENST00000297598.5 linkuse as main transcript	c.-45+655C>T		intron_variant		1	NM_018444.4	ENSP00000297598	P4	Q9P0J1-1

Frequencies

GnomAD3 genomes

AF:

0.0290

AC:

4411

AN:

152142

Hom.:

173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0879

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0334

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0224

Gnomad SAS

AF:

0.0114

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.0215

GnomAD4 exome

AF:

0.00540

AC:

6467

AN:

1197198

Hom.:

214

Cov.:

AF XY:

0.00507

AC XY:

3018

AN XY:

595030

show subpopulations

Gnomad4 AFR exome

AF:

0.0883

Gnomad4 AMR exome

AF:

0.0397

Gnomad4 ASJ exome

AF:

0.0000453

Gnomad4 EAS exome

AF:

0.0360

Gnomad4 SAS exome

AF:

0.00996

Gnomad4 FIN exome

AF:

0.0000231

Gnomad4 NFE exome

AF:

0.000185

Gnomad4 OTH exome

AF:

0.00896

GnomAD4 genome

AF:

0.0290

AC:

4421

AN:

152260

Hom.:

174

Cov.:

AF XY:

0.0289

AC XY:

2149

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0878

Gnomad4 AMR

AF:

0.0336

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0225

Gnomad4 SAS

AF:

0.0114

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.000594

Hom.:

Bravo

AF:

0.0334

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.97

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

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