rs147731055
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_002764.4(PRPS1):c.942C>T(p.Ser314=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000317 in 1,210,304 control chromosomes in the GnomAD database, including 1 homozygotes. There are 116 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00059 ( 0 hom., 18 hem., cov: 23)
Exomes 𝑓: 0.00029 ( 1 hom. 98 hem. )
Consequence
PRPS1
NM_002764.4 synonymous
NM_002764.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.35
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 Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
Variant X-107650017-C-T is Benign according to our data. Variant chrX-107650017-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 227882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-107650017-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=1.35 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 18 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRPS1 | NM_002764.4 | c.942C>T | p.Ser314= | synonymous_variant | 7/7 | ENST00000372435.10 | |
PRPS1 | NM_001204402.2 | c.330C>T | p.Ser110= | synonymous_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRPS1 | ENST00000372435.10 | c.942C>T | p.Ser314= | synonymous_variant | 7/7 | 1 | NM_002764.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000589 AC: 66AN: 112096Hom.: 0 Cov.: 23 AF XY: 0.000525 AC XY: 18AN XY: 34278
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GnomAD3 exomes AF: 0.000403 AC: 74AN: 183482Hom.: 0 AF XY: 0.000294 AC XY: 20AN XY: 67916
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GnomAD4 exome AF: 0.000290 AC: 318AN: 1098153Hom.: 1 Cov.: 30 AF XY: 0.000270 AC XY: 98AN XY: 363507
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GnomAD4 genome AF: 0.000588 AC: 66AN: 112151Hom.: 0 Cov.: 23 AF XY: 0.000524 AC XY: 18AN XY: 34343
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 17, 2015 | p.Ser314Ser in exon 7 of PRPS1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 33/87762 of chromoso mes (including 12 hemizygous individuals) by the Exome Aggregation Consortium (E xAC, http://exac.broadinstitute.org; dbSNP rs147731055). - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 15, 2016 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 26, 2021 | This variant is associated with the following publications: (PMID: 19377476) - |
Nephrolithiasis/nephrocalcinosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Charcot-Marie-Tooth Neuropathy X Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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