rs587781261
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PP2PP3_StrongPP5_Moderate
The NM_002764.4(PRPS1):c.337G>T(p.Ala113Ser) variant causes a missense change involving the alteration of a 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 Pathogenic (★).
Frequency
Genomes: not found (cov: 23)
Consequence
PRPS1
NM_002764.4 missense
NM_002764.4 missense
Scores
13
3
1
Clinical Significance
Conservation
PhyloP100: 9.48
Genes affected
PRPS1 (HGNC:9462): (phosphoribosyl pyrophosphate synthetase 1) This gene encodes an enzyme that catalyzes the phosphoribosylation of ribose 5-phosphate to 5-phosphoribosyl-1-pyrophosphate, which is necessary for purine metabolism and nucleotide biosynthesis. Defects in this gene are a cause of phosphoribosylpyrophosphate synthetase superactivity, Charcot-Marie-Tooth disease X-linked recessive type 5 and Arts Syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PM1
?
In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_002764.4
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, PRPS1
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.953
PP5
?
Variant X-107640932-G-T is Pathogenic according to our data. Variant chrX-107640932-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 140571.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-107640932-G-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRPS1 | NM_002764.4 | c.337G>T | p.Ala113Ser | missense_variant | 3/7 | ENST00000372435.10 | |
PRPS1 | NM_001204402.2 | c.-82-4245G>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRPS1 | ENST00000372435.10 | c.337G>T | p.Ala113Ser | missense_variant | 3/7 | 1 | NM_002764.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hearing loss, X-linked 1 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 03, 2014 | - - |
Pathogenic, criteria provided, single submitter | research | Molecular Genetics and RNA Biology, University of Milan | Oct 01, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;D
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Uncertain
D;.;D
REVEL
Pathogenic
Sift
Pathogenic
D;.;D
Sift4G
Uncertain
D;.;D
Polyphen
D;.;.
Vest4
MutPred
Gain of disorder (P = 0.0516);Gain of disorder (P = 0.0516);Gain of disorder (P = 0.0516);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at