chr5-142011947-C-T

Variant names:

• chr5-142011947-C-T
• rs1377973849
• NM_005471.5:c.89G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.00

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]

ACMG classification

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
GNPDA1	NM_005471.5	c.89G>A	p.Gly30Glu	missense_variant	Exon 2 of 7	ENST00000311337.11	NP_005462.1
GNPDA1	XM_005268348.2	c.176G>A	p.Gly59Glu	missense_variant	Exon 2 of 7		XP_005268405.1
GNPDA1	XM_006714747.2	c.89G>A	p.Gly30Glu	missense_variant	Exon 3 of 8		XP_006714810.1
GNPDA1	XM_047416582.1	c.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
GNPDA1	ENST00000311337.11	c.89G>A	p.Gly30Glu	missense_variant	Exon 2 of 7	1	NM_005471.5	ENSP00000311876.6

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

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

Other links and lift over

dbSNP: rs1377973849; hg19: chr5-141391512;