X-134473344-AT-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.823

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]

ACMG classification

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 GnomAd at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPRT1	NM_000194.3	c.28-14del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000298556.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPRT1	ENST00000298556.8	c.28-14del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000194.3	P1
HPRT1	ENST00000462974.5	n.186-14del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3
HPRT1	ENST00000475720.1			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

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

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

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

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

Submissions by phenotype

Lesch-Nyhan syndrome;C0268117:Partial hypoxanthine-guanine phosphoribosyltransferase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs754813142; hg19: chrX-133607374;