Variant 5-142006242-G-A 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_005471.5(GNPDA1):c.311C>T(p.Thr104Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GNPDA1
NM_005471.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.50

Variant links:

Genes affected

GNPDA1 (HGNC:4417): (glucosamine-6-phosphate deaminase 1) Glucosamine-6-phosphate deaminase (EC 3.5.99.6) is an allosteric enzyme that catalyzes the reversible conversion of D-glucosamine-6-phosphate into D-fructose-6-phosphate and ammonium (Arreola et al., 2003 [PubMed 12965206]).[supplied by OMIM, Jan 2010]

GNPDA1 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=0.1691294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GNPDA1	NM_005471.5 linkuse as main transcript	c.311C>T	p.Thr104Ile	missense_variant	4/7	ENST00000311337.11
GNPDA1	XM_005268348.2 linkuse as main transcript	c.398C>T	p.Thr133Ile	missense_variant	4/7
GNPDA1	XM_006714747.2 linkuse as main transcript	c.311C>T	p.Thr104Ile	missense_variant	5/8
GNPDA1	XM_047416582.1 linkuse as main transcript	c.311C>T	p.Thr104Ile	missense_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNPDA1	ENST00000311337.11 linkuse as main transcript	c.311C>T	p.Thr104Ile	missense_variant	4/7	1	NM_005471.5	P1	P46926-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461090

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726882

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Feb 27, 2023

The c.311C>T (p.T104I) alteration is located in exon 4 (coding exon 3) of the GNPDA1 gene. This alteration results from a C to T substitution at nucleotide position 311, causing the threonine (T) at amino acid position 104 to be replaced by an isoleucine (I). 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

0.17

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Benign

0.13

DEOGEN2

Benign

0.0039

T;T;T;T;T;T;T;.;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.076

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

D;.;.;.;D;D;D;D;D

M_CAP

Benign

0.0069

MetaRNN

Benign

0.17

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

2.2

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.21

Sift

Benign

1.0

T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.86

T;T;T;T;T;T;.;.;T

Polyphen

0.0

.;B;B;B;B;.;.;.;.

Vest4

0.65

MutPred

0.51

Loss of catalytic residue at T104 (P = 0.0631);Loss of catalytic residue at T104 (P = 0.0631);Loss of catalytic residue at T104 (P = 0.0631);Loss of catalytic residue at T104 (P = 0.0631);Loss of catalytic residue at T104 (P = 0.0631);Loss of catalytic residue at T104 (P = 0.0631);.;Loss of catalytic residue at T104 (P = 0.0631);Loss of catalytic residue at T104 (P = 0.0631);

MVP

0.39

MPC

0.49

ClinPred

0.75

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.62

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