chrX-134460350-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000194.3(HPRT1):​c.27+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 24)
Exomes 𝑓: 0.0000010 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control

Consequence

HPRT1
NM_000194.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.822
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant X-134460350-G-A is Benign according to our data. Variant chrX-134460350-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2951598.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HPRT1NM_000194.3 linkuse as main transcriptc.27+12G>A intron_variant ENST00000298556.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HPRT1ENST00000298556.8 linkuse as main transcriptc.27+12G>A intron_variant 1 NM_000194.3 P1
HPRT1ENST00000462974.5 linkuse as main transcript upstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000100
AC:
1
AN:
998971
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
321051
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000126
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
24

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Lesch-Nyhan syndrome;C0268117:Partial hypoxanthine-guanine phosphoribosyltransferase deficiency Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeSep 04, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
11
DANN
Benign
0.88
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-133594380; API