rs1468266

Variant names:

• chrX-134482828-T-A
• rs1468266
• NM_000194.3:c.319-3637T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000194.3(HPRT1):​c.319-3637T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 109,413 control chromosomes in the GnomAD database, including 1,591 homozygotes. There are 5,116 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (1591 hom., 5116 hem., cov: 22)
• Consequence: HPRT1 NM_000194.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606
• Publications: 2 publications found

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]

HPRT1 Gene-Disease associations (from GenCC):

• Lesch-Nyhan syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics, Orphanet
• hypoxanthine guanine phosphoribosyltransferase partial deficiency

  Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000194.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPRT1	NM_000194.3	MANE Select	c.319-3637T>A		intron	N/A	NP_000185.1	A0A140VJL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPRT1	ENST00000298556.8	TSL:1 MANE Select	c.319-3637T>A		intron	N/A	ENSP00000298556.7	P00492
	HPRT1	ENST00000969780.1		c.364-3637T>A		intron	N/A	ENSP00000639839.1
	HPRT1	ENST00000969779.1		c.319-3637T>A		intron	N/A	ENSP00000639838.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 19153 AN: 109360 Hom.: 1591 Cov.: 22

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.0532

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.000575

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.171

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.175 AC: 19158 AN: 109413 Hom.: 1591 Cov.: 22 AF XY: 0.160 AC XY: 5116 AN XY: 31971

African (AFR) AF: 0.291 AC: 8739 AN: 30019

American (AMR) AF: 0.105 AC: 1060 AN: 10063

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 295 AN: 2627

East Asian (EAS) AF: 0.000577 AC: 2 AN: 3469

South Asian (SAS) AF: 0.0600 AC: 152 AN: 2534

European-Finnish (FIN) AF: 0.151 AC: 862 AN: 5700

Middle Eastern (MID) AF: 0.107 AC: 23 AN: 214

European-Non Finnish (NFE) AF: 0.147 AC: 7739 AN: 52629

Other (OTH) AF: 0.169 AC: 250 AN: 1481

Alfa AF: 0.164 Hom.: 927

Bravo AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.82
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1468266; hg19: chrX-133616858;