chr3-155931774-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_003875.3(GMPS):c.1570C>T(p.Arg524Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000007 in 1,429,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000070 ( 0 hom. )
Consequence
GMPS
NM_003875.3 missense
NM_003875.3 missense
Scores
14
3
2
Clinical Significance
Conservation
PhyloP100: 3.67
Genes affected
GMPS (HGNC:4378): (guanine monophosphate synthase) In the de novo synthesis of purine nucleotides, IMP is the branch point metabolite at which point the pathway diverges to the synthesis of either guanine or adenine nucleotides. In the guanine nucleotide pathway, there are 2 enzymes involved in converting IMP to GMP, namely IMP dehydrogenase (IMPD1), which catalyzes the oxidation of IMP to XMP, and GMP synthetase, which catalyzes the amination of XMP to GMP. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.981
BS2
High AC in GnomAdExome4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GMPS | NM_003875.3 | c.1570C>T | p.Arg524Cys | missense_variant | 13/16 | ENST00000496455.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GMPS | ENST00000496455.7 | c.1570C>T | p.Arg524Cys | missense_variant | 13/16 | 1 | NM_003875.3 | P1 | |
GMPS | ENST00000295920.7 | c.1273C>T | p.Arg425Cys | missense_variant | 11/14 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000667 AC: 1AN: 149932Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000122 AC: 3AN: 245894Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133540
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GnomAD4 exome AF: 0.00000703 AC: 9AN: 1279388Hom.: 0 Cov.: 19 AF XY: 0.00000619 AC XY: 4AN XY: 646202
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GnomAD4 genome AF: 0.00000667 AC: 1AN: 149932Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 72896
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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 submitter | clinical testing | Ambry Genetics | Nov 13, 2023 | The c.1570C>T (p.R524C) alteration is located in exon 13 (coding exon 13) of the GMPS gene. This alteration results from a C to T substitution at nucleotide position 1570, causing the arginine (R) at amino acid position 524 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Loss of sheet (P = 0.1158);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at