rs869025594
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP2PP3_ModeratePP5
The NM_002764.4(PRPS1):c.46T>C(p.Ser16Pro) 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. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S16F) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 22)
Consequence
PRPS1
NM_002764.4 missense
NM_002764.4 missense
Scores
10
4
3
Clinical Significance
Conservation
PhyloP100: 7.07
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 Likely_pathogenic. Variant got 8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chrX-107628675-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 446161.Status of the report is no_assertion_criteria_provided, 0 stars.
PP2
?
Missense variant where missense usually causes diseases, PRPS1
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.892
PP5
?
Variant X-107628674-T-C is Pathogenic according to our data. Variant chrX-107628674-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 223101.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-107628674-T-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRPS1 | NM_002764.4 | c.46T>C | p.Ser16Pro | missense_variant | 1/7 | ENST00000372435.10 | |
PRPS1 | NM_001204402.2 | c.-159T>C | 5_prime_UTR_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRPS1 | ENST00000372435.10 | c.46T>C | p.Ser16Pro | missense_variant | 1/7 | 1 | NM_002764.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease X-linked recessive 5 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 23, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;.;D;D
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;.;T;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;.;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;.;.;N;D
REVEL
Pathogenic
Sift
Uncertain
D;.;.;D;D
Sift4G
Uncertain
D;.;.;.;D
Polyphen
P;.;.;.;.
Vest4
MutPred
Loss of ubiquitination at K18 (P = 0.052);Loss of ubiquitination at K18 (P = 0.052);Loss of ubiquitination at K18 (P = 0.052);Loss of ubiquitination at K18 (P = 0.052);Loss of ubiquitination at K18 (P = 0.052);
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