14-24236089-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001002002.3(GMPR2):​c.414T>G​(p.Phe138Leu) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GMPR2
NM_001002002.3 missense

Scores

6
6
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0230

Publications

2 publications found
Variant links:
Genes affected
GMPR2 (HGNC:4377): (guanosine monophosphate reductase 2) This gene encodes an enzyme that catalyzes the irreversible and NADPH-dependent reductive deamination of guanosine monophosphate (GMP) to inosine monophosphate (IMP). The protein also functions in the re-utilization of free intracellular bases and purine nucleosides. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GMPR2NM_001002002.3 linkc.414T>G p.Phe138Leu missense_variant Exon 5 of 10 ENST00000399440.7 NP_001002002.1 Q9P2T1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GMPR2ENST00000399440.7 linkc.414T>G p.Phe138Leu missense_variant Exon 5 of 10 1 NM_001002002.3 ENSP00000382369.2 Q9P2T1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
3
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
Jun 03, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.468T>G (p.F156L) alteration is located in exon 4 (coding exon 4) of the GMPR2 gene. This alteration results from a T to G substitution at nucleotide position 468, causing the phenylalanine (F) at amino acid position 156 to be replaced by a leucine (L). 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
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.77
.;D;D;.;D;D;D;.;.;.
Eigen
Benign
0.076
Eigen_PC
Benign
0.012
FATHMM_MKL
Uncertain
0.85
D
M_CAP
Uncertain
0.098
D
MetaRNN
Pathogenic
0.79
D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.10
T
MutationAssessor
Benign
2.0
.;M;M;.;.;.;M;.;.;.
PhyloP100
-0.023
PrimateAI
Uncertain
0.75
T
PROVEAN
Pathogenic
-5.4
.;D;D;.;D;D;D;D;D;D
REVEL
Pathogenic
0.66
Sift
Benign
0.14
.;T;T;.;T;T;T;T;T;T
Sift4G
Benign
0.11
T;T;T;T;T;T;T;T;T;T
Polyphen
0.99, 0.99
.;D;D;.;.;.;D;D;.;.
Vest4
0.73
MutPred
0.64
Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);.;.;.;Loss of loop (P = 0.0804);.;.;.;
MVP
0.82
MPC
0.42
ClinPred
0.99
D
GERP RS
0.60
PromoterAI
0.0045
Neutral
Varity_R
0.90
gMVP
0.83
Mutation Taster
=16/84
disease causing

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

Other links and lift over

dbSNP: rs74976241; hg19: chr14-24705295; API