rs147731055

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

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.35
Variant links:
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
PRPS1NM_002764.4 linkuse as main transcriptc.942C>T p.Ser314= synonymous_variant 7/7 ENST00000372435.10
PRPS1NM_001204402.2 linkuse as main transcriptc.330C>T p.Ser110= synonymous_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRPS1ENST00000372435.10 linkuse as main transcriptc.942C>T p.Ser314= synonymous_variant 7/71 NM_002764.4 P1P60891-1

Frequencies

GnomAD3 genomes
AF:
0.000589
AC:
66
AN:
112096
Hom.:
0
Cov.:
23
AF XY:
0.000525
AC XY:
18
AN XY:
34278
show subpopulations
Gnomad AFR
AF:
0.000875
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00190
Gnomad ASJ
AF:
0.00264
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000207
Gnomad OTH
AF:
0.000667
GnomAD3 exomes
AF:
0.000403
AC:
74
AN:
183482
Hom.:
0
AF XY:
0.000294
AC XY:
20
AN XY:
67916
show subpopulations
Gnomad AFR exome
AF:
0.00137
Gnomad AMR exome
AF:
0.000547
Gnomad ASJ exome
AF:
0.00267
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000232
Gnomad OTH exome
AF:
0.000441
GnomAD4 exome
AF:
0.000290
AC:
318
AN:
1098153
Hom.:
1
Cov.:
30
AF XY:
0.000270
AC XY:
98
AN XY:
363507
show subpopulations
Gnomad4 AFR exome
AF:
0.000871
Gnomad4 AMR exome
AF:
0.000625
Gnomad4 ASJ exome
AF:
0.00315
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000194
Gnomad4 OTH exome
AF:
0.000955
GnomAD4 genome
AF:
0.000588
AC:
66
AN:
112151
Hom.:
0
Cov.:
23
AF XY:
0.000524
AC XY:
18
AN XY:
34343
show subpopulations
Gnomad4 AFR
AF:
0.000873
Gnomad4 AMR
AF:
0.00190
Gnomad4 ASJ
AF:
0.00264
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000207
Gnomad4 OTH
AF:
0.000659
Alfa
AF:
0.00139
Hom.:
9
Bravo
AF:
0.00112
EpiCase
AF:
0.000709
EpiControl
AF:
0.000296

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 submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMay 17, 2015p.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 submitterclinical testingEurofins Ntd Llc (ga)Jul 15, 2016- -
not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2020- -
Benign, criteria provided, single submitterclinical testingGeneDxMar 26, 2021This variant is associated with the following publications: (PMID: 19377476) -
Nephrolithiasis/nephrocalcinosis Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJul 11, 2019This 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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 24, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.35
CADD
Benign
9.0
DANN
Benign
0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147731055; hg19: chrX-106893247; API