chr6-16278873-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006877.4(GMPR):​c.637A>G​(p.Lys213Glu) variant causes a missense change. 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: 33)

Consequence

GMPR
NM_006877.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.21
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32805598).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GMPRNM_006877.4 linkuse as main transcriptc.637A>G p.Lys213Glu missense_variant 6/9 ENST00000259727.5
GMPRXM_047418656.1 linkuse as main transcriptc.637A>G p.Lys213Glu missense_variant 6/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GMPRENST00000259727.5 linkuse as main transcriptc.637A>G p.Lys213Glu missense_variant 6/91 NM_006877.4 P1
GMPRENST00000543191.5 linkuse as main transcriptn.150-6920A>G intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsSep 28, 2021The c.637A>G (p.K213E) alteration is located in exon 6 (coding exon 6) of the GMPR gene. This alteration results from a A to G substitution at nucleotide position 637, causing the lysine (K) at amino acid position 213 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
0.22
BayesDel_addAF
Uncertain
0.062
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
23
DANN
Benign
0.94
DEOGEN2
Uncertain
0.51
D
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.64
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.057
D
MetaRNN
Benign
0.33
T
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-0.89
N
REVEL
Uncertain
0.41
Sift
Benign
0.033
D
Sift4G
Uncertain
0.018
D
Polyphen
0.044
B
Vest4
0.51
MutPred
0.46
Loss of glycosylation at K213 (P = 0.0453);
MVP
0.58
MPC
0.15
ClinPred
0.73
D
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.81
gMVP
0.79

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: chr6-16279104; API