rs137852494
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP3_StrongPP5
The NM_000194.3(HPRT1):āc.151C>Gā(p.Arg51Gly) 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,other (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R51P) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 22)
Exomes š: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
HPRT1
NM_000194.3 missense
NM_000194.3 missense
Scores
9
6
2
Clinical Significance
Conservation
PhyloP100: 3.75
Genes affected
HPRT1 (HGNC:5157): (hypoxanthine phosphoribosyltransferase 1) The protein encoded by this gene is a transferase, which catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate via transfer of the 5-phosphoribosyl group from 5-phosphoribosyl 1-pyrophosphate. This enzyme plays a central role in the generation of purine nucleotides through the purine salvage pathway. Mutations in this gene result in Lesch-Nyhan syndrome or gout.[provided by RefSeq, Jun 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PM1
?
In a hotspot region, there are 7 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_000194.3
PM2
?
Very rare variant in population databases, with high coverage;
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.981
PP5
?
Variant X-134475197-C-G is Pathogenic according to our data. Variant chrX-134475197-C-G is described in ClinVar as [Pathogenic, other]. Clinvar id is 10059.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HPRT1 | NM_000194.3 | c.151C>G | p.Arg51Gly | missense_variant | 3/9 | ENST00000298556.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HPRT1 | ENST00000298556.8 | c.151C>G | p.Arg51Gly | missense_variant | 3/9 | 1 | NM_000194.3 | P1 | |
HPRT1 | ENST00000462974.5 | n.309C>G | non_coding_transcript_exon_variant | 3/8 | 3 | ||||
HPRT1 | ENST00000475720.1 | n.109C>G | non_coding_transcript_exon_variant | 2/8 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1090654Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 356592
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1090654
Hom.:
Cov.:
28
AF XY:
AC XY:
0
AN XY:
356592
Gnomad4 AFR exome
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Gnomad4 FIN exome
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GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Pathogenic; other
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Partial hypoxanthine-guanine phosphoribosyltransferase deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 1983 | - - |
HPRT TORONTO Other:1
other, no assertion criteria provided | literature only | OMIM | Sep 10, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of stability (P = 0.0244);
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