rs756853882
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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):āc.60T>Cā(p.Ala20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000827 in 1,209,376 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0000090 ( 0 hom., 0 hem., cov: 23)
Exomes š: 0.0000082 ( 0 hom. 2 hem. )
Consequence
PRPS1
NM_002764.4 synonymous
NM_002764.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.782
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=-0.45).
BP6
?
Variant X-107628688-T-C is Benign according to our data. Variant chrX-107628688-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 543929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.782 with no splicing effect.
BS2
?
High Hemizygotes in GnomAdExome4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRPS1 | NM_002764.4 | c.60T>C | p.Ala20= | synonymous_variant | 1/7 | ENST00000372435.10 | |
PRPS1 | NM_001204402.2 | c.-145T>C | 5_prime_UTR_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRPS1 | ENST00000372435.10 | c.60T>C | p.Ala20= | synonymous_variant | 1/7 | 1 | NM_002764.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000900 AC: 1AN: 111147Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33335
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GnomAD3 exomes AF: 0.0000218 AC: 4AN: 183493Hom.: 0 AF XY: 0.0000147 AC XY: 1AN XY: 67933
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GnomAD4 exome AF: 0.00000820 AC: 9AN: 1098229Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 2AN XY: 363591
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GnomAD4 genome ? AF: 0.00000900 AC: 1AN: 111147Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33335
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
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
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 28, 2023 | - - |
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