Variant 16-70127360-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_017990.5(PDPR):c.328T>C(p.Tyr110His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 10794 hom., cov: 46)

Exomes 𝑓: 0.53 ( 104253 hom. )

Failed GnomAD Quality Control

Consequence

PDPR
NM_017990.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.51

Variant links:

Genes affected

PDPR (HGNC:30264): (pyruvate dehydrogenase phosphatase regulatory subunit) Pyruvate dehydrogenase complex (PDC) catalyzes the oxidative decarboxylation of pyruvate and links glycolysis to the tricarboxylic acid cycle and fatty acid synthesis. The dephosphorylation and reactivation of PDC is catalyzed by pyruvate dehydrogenase phosphatase (PDP). The dimeric PDP has a catalytic subunit and a regulatory subunit. This gene encodes the FAD-containing regulatory subunit of PDP. The encoded protein acts to decrease the sensitivity of the PDP catalytic subunit to magnesium ions. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017]

PDPR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028902888).

BP6

Variant 16-70127360-T-C is Benign according to our data. Variant chr16-70127360-T-C is described in ClinVar as [Benign]. Clinvar id is 768784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDPR	NM_017990.5 linkuse as main transcript	c.328T>C	p.Tyr110His	missense_variant	4/19	ENST00000288050.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDPR	ENST00000288050.9 linkuse as main transcript	c.328T>C	p.Tyr110His	missense_variant	4/19	1	NM_017990.5	P1	Q8NCN5-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

79812

AN:

149404

Hom.:

10779

Cov.:

FAILED QC

Gnomad AFR

AF:

0.485

Gnomad AMI

AF:

0.601

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.540

Gnomad EAS

AF:

0.450

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.597

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.554

Gnomad OTH

AF:

0.538

GnomAD3 exomes

AF:

0.456

AC:

82073

AN:

179888

Hom.:

13524

AF XY:

0.444

AC XY:

42961

AN XY:

96760

show subpopulations

Gnomad AFR exome

AF:

0.391

Gnomad AMR exome

AF:

0.544

Gnomad ASJ exome

AF:

0.394

Gnomad EAS exome

AF:

0.377

Gnomad SAS exome

AF:

0.293

Gnomad FIN exome

AF:

0.573

Gnomad NFE exome

AF:

0.477

Gnomad OTH exome

AF:

0.480

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.531

AC:

642335

AN:

1208842

Hom.:

104253

Cov.:

AF XY:

0.525

AC XY:

316063

AN XY:

601716

show subpopulations

Gnomad4 AFR exome

AF:

0.448

Gnomad4 AMR exome

AF:

0.580

Gnomad4 ASJ exome

AF:

0.513

Gnomad4 EAS exome

AF:

0.449

Gnomad4 SAS exome

AF:

0.404

Gnomad4 FIN exome

AF:

0.605

Gnomad4 NFE exome

AF:

0.542

Gnomad4 OTH exome

AF:

0.520

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.534

AC:

79872

AN:

149516

Hom.:

10794

Cov.:

AF XY:

0.534

AC XY:

39021

AN XY:

73058

show subpopulations

Gnomad4 AFR

AF:

0.485

Gnomad4 AMR

AF:

0.583

Gnomad4 ASJ

AF:

0.540

Gnomad4 EAS

AF:

0.450

Gnomad4 SAS

AF:

0.451

Gnomad4 FIN

AF:

0.597

Gnomad4 NFE

AF:

0.554

Gnomad4 OTH

AF:

0.538

Alfa

AF:

0.503

Hom.:

1846

ExAC

AF:

0.416

AC:

50215

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	Labcorp Genetics (formerly Invitae), Labcorp	May 25, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.017

T;T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.023

.;T;T

MetaRNN

Benign

0.0029

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.34

N;.;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.38

PROVEAN

Benign

1.1

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.30

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.058

MPC

0.58

ClinPred

0.011

GERP RS

3.8

Varity_R

0.036

gMVP

0.47

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

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