Variant chr16-70132187-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017990.5(PDPR):c.884A>C(p.Asn295Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000206 in 1,613,166 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00012 ( 0 hom., cov: 46)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

PDPR
NM_017990.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12665576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDPR	NM_017990.5 linkuse as main transcript	c.884A>C	p.Asn295Thr	missense_variant	9/19	ENST00000288050.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDPR	ENST00000288050.9 linkuse as main transcript	c.884A>C	p.Asn295Thr	missense_variant	9/19	1	NM_017990.5	P1	Q8NCN5-1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152246

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:

0.000207

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000309

AC:

AN:

249148

Hom.:

AF XY:

0.000348

AC XY:

AN XY:

135170

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.000650

Gnomad NFE exome

AF:

0.000416

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.000214

AC:

313

AN:

1460920

Hom.:

Cov.:

AF XY:

0.000222

AC XY:

161

AN XY:

726790

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.000974

Gnomad4 NFE exome

AF:

0.000182

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000125

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74380

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:

0.000207

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000918

Hom.:

ExAC

AF:

0.000480

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

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

Nov 15, 2021

The c.884A>C (p.N295T) alteration is located in exon 9 (coding exon 7) of the PDPR gene. This alteration results from a A to C substitution at nucleotide position 884, causing the asparagine (N) at amino acid position 295 to be replaced by a threonine (T). 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

0.21

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.032

T;T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

0.021

FATHMM_MKL

Benign

0.56

LIST_S2

Uncertain

0.92

.;D;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

-0.22

N;.;N

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.72

N;N;N

REVEL

Benign

0.23

Sift

Benign

0.13

T;T;T

Sift4G

Uncertain

0.028

D;D;D

Polyphen

0.0040

B;.;B

Vest4

0.53

MVP

0.77

MPC

0.54

ClinPred

0.031

GERP RS

4.0

Varity_R

0.12

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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