6-16254707-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_006877.4(GMPR):​c.437G>C​(p.Arg146Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

GMPR
NM_006877.4 missense

Scores

14
4
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.77
Variant links:
Genes affected
GMPR (HGNC:4376): (guanosine monophosphate reductase) This gene encodes an enzyme that catalyzes the irreversible and NADPH-dependent reductive deamination of GMP to IMP. The protein also functions in the re-utilization of free intracellular bases and purine nucleosides.[provided by RefSeq, Oct 2009]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.967

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GMPRNM_006877.4 linkc.437G>C p.Arg146Pro missense_variant Exon 4 of 9 ENST00000259727.5 NP_006868.3 P36959
GMPRXM_047418656.1 linkc.437G>C p.Arg146Pro missense_variant Exon 4 of 9 XP_047274612.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GMPRENST00000259727.5 linkc.437G>C p.Arg146Pro missense_variant Exon 4 of 9 1 NM_006877.4 ENSP00000259727.4 P36959

Frequencies

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.41
D
BayesDel_noAF
Pathogenic
0.35
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.93
D
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.91
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Pathogenic
0.33
D
MetaRNN
Pathogenic
0.97
D
MetaSVM
Uncertain
0.73
D
MutationAssessor
Pathogenic
4.3
H
PrimateAI
Uncertain
0.58
T
PROVEAN
Pathogenic
-6.1
D
REVEL
Pathogenic
0.74
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0040
D
Polyphen
1.0
D
Vest4
0.87
MutPred
0.79
Gain of ubiquitination at K143 (P = 0.0704);
MVP
0.95
MPC
0.53
ClinPred
1.0
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.99
gMVP
0.98

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-16254938; API