chr5-142011947-C-T

Variant summary

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

The NM_005471.5(GNPDA1):​c.89G>A​(p.Gly30Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

GNPDA1
NM_005471.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00
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]

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=0.23300865).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GNPDA1NM_005471.5 linkc.89G>A p.Gly30Glu missense_variant Exon 2 of 7 ENST00000311337.11 NP_005462.1 P46926-1
GNPDA1XM_005268348.2 linkc.176G>A p.Gly59Glu missense_variant Exon 2 of 7 XP_005268405.1
GNPDA1XM_006714747.2 linkc.89G>A p.Gly30Glu missense_variant Exon 3 of 8 XP_006714810.1 P46926-1
GNPDA1XM_047416582.1 linkc.89G>A p.Gly30Glu missense_variant Exon 3 of 8 XP_047272538.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GNPDA1ENST00000311337.11 linkc.89G>A p.Gly30Glu missense_variant Exon 2 of 7 1 NM_005471.5 ENSP00000311876.6 P46926-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 22, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.89G>A (p.G30E) alteration is located in exon 2 (coding exon 1) of the GNPDA1 gene. This alteration results from a G to A substitution at nucleotide position 89, causing the glycine (G) at amino acid position 30 to be replaced by a glutamic acid (E). 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
0.31
BayesDel_addAF
Benign
-0.0078
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0057
T;T;T;T;T;T;T;.;.
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.0067
FATHMM_MKL
Benign
0.72
D
LIST_S2
Uncertain
0.90
D;.;.;.;D;D;D;D;D
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.23
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.3
.;L;L;L;L;.;.;.;.
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.77
N;N;N;N;N;N;N;N;N
REVEL
Benign
0.14
Sift
Uncertain
0.015
D;D;D;D;D;D;D;D;D
Sift4G
Benign
0.29
T;T;T;T;T;T;.;.;T
Polyphen
0.0040
.;B;B;B;B;.;.;.;.
Vest4
0.37
MutPred
0.39
Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);
MVP
0.50
MPC
0.62
ClinPred
0.83
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.53
gMVP
0.80

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.

Other links and lift over

dbSNP: rs1377973849; hg19: chr5-141391512; API