Variant chr16-70129108-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017990.5(PDPR):c.593C>G(p.Ala198Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000656 in 152,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 46)

Consequence

PDPR
NM_017990.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35517204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDPR	NM_017990.5 linkuse as main transcript	c.593C>G	p.Ala198Gly	missense_variant	6/19	ENST00000288050.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDPR	ENST00000288050.9 linkuse as main transcript	c.593C>G	p.Ala198Gly	missense_variant	6/19	1	NM_017990.5	P1	Q8NCN5-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152294

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152412

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74534

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2022

The c.593C>G (p.A198G) alteration is located in exon 6 (coding exon 4) of the PDPR gene. This alteration results from a C to G substitution at nucleotide position 593, causing the alanine (A) at amino acid position 198 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.038

T;T;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

.;T;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.46

N;.;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.13

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.51

T;T;T

Sift4G

Benign

0.54

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.43

MutPred

0.78

Gain of glycosylation at S197 (P = 0.0559);.;Gain of glycosylation at S197 (P = 0.0559);

MVP

0.68

MPC

0.45

ClinPred

0.76

GERP RS

3.5

Varity_R

0.16

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over