Variant 1-10400558-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002631.4(PGD):c.250T>G(p.Phe84Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,461,144 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PGD
NM_002631.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.94

Variant links:

Genes affected

PGD (HGNC:8891): (phosphogluconate dehydrogenase) 6-phosphogluconate dehydrogenase is the second dehydrogenase in the pentose phosphate shunt. Deficiency of this enzyme is generally asymptomatic, and the inheritance of this disorder is autosomal dominant. Hemolysis results from combined deficiency of 6-phosphogluconate dehydrogenase and 6-phosphogluconolactonase suggesting a synergism of the two enzymopathies. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

PGD links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGD	NM_002631.4 link	c.250T>G	p.Phe84Val	missense_variant	3/13	ENST00000270776.13	NP_002622.2	P52209-1
PGD	NM_001304452.2 link	c.211T>G	p.Phe71Val	missense_variant	3/13		NP_001291381.1	P52209-2
PGD	NM_001304451.2 link	c.250T>G	p.Phe84Val	missense_variant	3/12		NP_001291380.1	P52209B4E2U0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGD	ENST00000270776.13 link	c.250T>G	p.Phe84Val	missense_variant	3/13	1	NM_002631.4	ENSP00000270776.8		P52209-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1461144

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000172

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

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 29, 2023

The c.250T>G (p.F84V) alteration is located in exon 3 (coding exon 3) of the PGD gene. This alteration results from a T to G substitution at nucleotide position 250, causing the phenylalanine (F) at amino acid position 84 to be replaced by a valine (V). 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

Uncertain

0.34

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T;T

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.4

.;L;.

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.8

.;D;.

REVEL

Uncertain

0.41

Sift

Uncertain

0.023

.;D;.

Sift4G

Benign

0.99

T;T;T

Polyphen

0.94

.;P;.

Vest4

0.79

MVP

0.79

MPC

1.1

ClinPred

0.99

GERP RS

4.9

Varity_R

0.85

gMVP

0.84

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