X-134486475-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PP3_ModeratePP5_Moderate
The NM_000194.3(HPRT1):c.329C>T(p.Ser110Leu) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_000194.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HPRT1 | NM_000194.3 | c.329C>T | p.Ser110Leu | missense_variant | Exon 4 of 9 | ENST00000298556.8 | NP_000185.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HPRT1 | ENST00000298556.8 | c.329C>T | p.Ser110Leu | missense_variant | Exon 4 of 9 | 1 | NM_000194.3 | ENSP00000298556.7 | ||
HPRT1 | ENST00000462974.5 | n.487C>T | non_coding_transcript_exon_variant | Exon 4 of 8 | 3 | |||||
HPRT1 | ENST00000475720.1 | n.287C>T | non_coding_transcript_exon_variant | Exon 3 of 8 | 3 |
Frequencies
GnomAD3 genomes Cov.: 20
GnomAD4 exome AF: 0.00000198 AC: 2AN: 1011610Hom.: 0 Cov.: 19 AF XY: 0.00000328 AC XY: 1AN XY: 304498
GnomAD4 genome Cov.: 20
ClinVar
Submissions by phenotype
Partial hypoxanthine-guanine phosphoribosyltransferase deficiency Pathogenic:1
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Lesch-Nyhan syndrome;C0268117:Partial hypoxanthine-guanine phosphoribosyltransferase deficiency Pathogenic:1
Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 110 of the HPRT1 protein (p.Ser110Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypoxanthine-guanine phosphoribosyltransferase deficiency (PMID: 3198771). This variant is also known as HPRT(London). ClinVar contains an entry for this variant (Variation ID: 10038). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects HPRT1 function (PMID: 22157001). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. -
HPRT LONDON Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at