Variant chr16-70120577-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017990.5(PDPR):c.85A>G(p.Thr29Ala) 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 not provided (no stars).

Frequency

Genomes: 𝑓 0.025 ( 7 hom., cov: 33)

Exomes 𝑓: 0.063 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

PDPR
NM_017990.5 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.343

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034724474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDPR	NM_017990.5 linkuse as main transcript	c.85A>G	p.Thr29Ala	missense_variant	3/19	ENST00000288050.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDPR	ENST00000288050.9 linkuse as main transcript	c.85A>G	p.Thr29Ala	missense_variant	3/19	1	NM_017990.5	P1	Q8NCN5-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

2675

AN:

108074

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0339

Gnomad AMI

AF:

0.0695

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.0151

Gnomad EAS

AF:

0.0192

Gnomad SAS

AF:

0.0200

Gnomad FIN

AF:

0.0325

Gnomad MID

AF:

0.0400

Gnomad NFE

AF:

0.0215

Gnomad OTH

AF:

0.0286

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0629

AC:

57401

AN:

913124

Hom.:

Cov.:

AF XY:

0.0573

AC XY:

26625

AN XY:

464946

show subpopulations

Gnomad4 AFR exome

AF:

0.0489

Gnomad4 AMR exome

AF:

0.00503

Gnomad4 ASJ exome

AF:

0.0200

Gnomad4 EAS exome

AF:

0.00692

Gnomad4 SAS exome

AF:

0.0117

Gnomad4 FIN exome

AF:

0.0524

Gnomad4 NFE exome

AF:

0.0786

Gnomad4 OTH exome

AF:

0.0492

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0247

AC:

2676

AN:

108206

Hom.:

Cov.:

AF XY:

0.0240

AC XY:

1281

AN XY:

53454

show subpopulations

Gnomad4 AFR

AF:

0.0338

Gnomad4 AMR

AF:

0.0121

Gnomad4 ASJ

AF:

0.0151

Gnomad4 EAS

AF:

0.0192

Gnomad4 SAS

AF:

0.0203

Gnomad4 FIN

AF:

0.0325

Gnomad4 NFE

AF:

0.0215

Gnomad4 OTH

AF:

0.0296

Alfa

AF:

0.0438

Hom.:

ExAC

AF:

0.0476

AC:

5769

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

not provided, no classification provided

literature only

Department of Mental Retardation and Birth Defect Research, National Center of Neurology and Psychiatry

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.041

DANN

Benign

0.20

DEOGEN2

Benign

0.0053

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.11

.;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.20

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.060

N;N

REVEL

Benign

0.023

Sift

Benign

0.61

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.0

B;B

Vest4

0.054

MPC

0.43

ClinPred

0.00091

GERP RS

-5.2

Varity_R

0.017

gMVP

0.20

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