chrX-134473344-AT-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_000194.3(HPRT1):​c.28-14del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000173 in 937,769 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 46 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 5 hem., cov: 23)
Exomes 𝑓: 0.00018 ( 0 hom. 41 hem. )

Consequence

HPRT1
NM_000194.3 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.823
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6
Variant X-134473344-AT-A is Benign according to our data. Variant chrX-134473344-AT-A is described in ClinVar as [Benign]. Clinvar id is 2043338.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HPRT1NM_000194.3 linkuse as main transcriptc.28-14del splice_polypyrimidine_tract_variant, intron_variant ENST00000298556.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HPRT1ENST00000298556.8 linkuse as main transcriptc.28-14del splice_polypyrimidine_tract_variant, intron_variant 1 NM_000194.3 P1
HPRT1ENST00000462974.5 linkuse as main transcriptn.186-14del splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant 3
HPRT1ENST00000475720.1 linkuse as main transcript upstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.000134
AC:
15
AN:
112104
Hom.:
0
Cov.:
23
AF XY:
0.000146
AC XY:
5
AN XY:
34266
show subpopulations
Gnomad AFR
AF:
0.0000324
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00151
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000169
Gnomad OTH
AF:
0.000663
GnomAD3 exomes
AF:
0.000115
AC:
21
AN:
183048
Hom.:
0
AF XY:
0.000177
AC XY:
12
AN XY:
67606
show subpopulations
Gnomad AFR exome
AF:
0.0000761
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00107
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000158
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000110
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000178
AC:
147
AN:
825665
Hom.:
0
Cov.:
15
AF XY:
0.000173
AC XY:
41
AN XY:
236881
show subpopulations
Gnomad4 AFR exome
AF:
0.0000470
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000906
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000164
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000190
Gnomad4 OTH exome
AF:
0.000244
GnomAD4 genome
AF:
0.000134
AC:
15
AN:
112104
Hom.:
0
Cov.:
23
AF XY:
0.000146
AC XY:
5
AN XY:
34266
show subpopulations
Gnomad4 AFR
AF:
0.0000324
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00151
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000169
Gnomad4 OTH
AF:
0.000663
Alfa
AF:
0.000260
Hom.:
2
Bravo
AF:
0.0000945

ClinVar

Significance: 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
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs754813142; hg19: chrX-133607374; API