Variant 5-142006264-T-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_005471.5(GNPDA1):c.289A>G(p.Ile97Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,750 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: 6.8e-7 ( 0 hom. )

Consequence

GNPDA1
NM_005471.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.98

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:

GNPDA1 (HGNC:):

GNPDA1 links:

Genome browser will be placed here

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=0.14958265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNPDA1	NM_005471.5 linkuse as main transcript	c.289A>G	p.Ile97Val	missense_variant	4/7	ENST00000311337.11	NP_005462.1	P46926-1
GNPDA1	XM_005268348.2 linkuse as main transcript	c.376A>G	p.Ile126Val	missense_variant	4/7		XP_005268405.1
GNPDA1	XM_006714747.2 linkuse as main transcript	c.289A>G	p.Ile97Val	missense_variant	5/8		XP_006714810.1	P46926-1
GNPDA1	XM_047416582.1 linkuse as main transcript	c.289A>G	p.Ile97Val	missense_variant	5/8		XP_047272538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNPDA1	ENST00000311337.11 linkuse as main transcript	c.289A>G	p.Ile97Val	missense_variant	4/7	1	NM_005471.5	ENSP00000311876.6		P46926-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251474

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461750

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727180

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Jun 29, 2023

The c.289A>G (p.I97V) alteration is located in exon 4 (coding exon 3) of the GNPDA1 gene. This alteration results from a A to G substitution at nucleotide position 289, causing the isoleucine (I) at amino acid position 97 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

Benign

0.066

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.010

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

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.097

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

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

M_CAP

Benign

0.0093

MetaRNN

Benign

0.15

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

.;L;L;L;L;.;.;.;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.17

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

REVEL

Benign

0.038

Sift

Benign

0.45

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

Sift4G

Benign

0.72

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

Polyphen

0.0

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

Vest4

0.36

MutPred

0.58

Loss of ubiquitination at K95 (P = 0.2094);Loss of ubiquitination at K95 (P = 0.2094);Loss of ubiquitination at K95 (P = 0.2094);Loss of ubiquitination at K95 (P = 0.2094);Loss of ubiquitination at K95 (P = 0.2094);Loss of ubiquitination at K95 (P = 0.2094);.;Loss of ubiquitination at K95 (P = 0.2094);Loss of ubiquitination at K95 (P = 0.2094);

MVP

0.40

MPC

0.41

ClinPred

0.21

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.53

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