chrX-134482828-T-A

Position:

• chrX-134482828-T-A

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPRT1	NM_000194.3	c.319-3637T>A		intron_variant		ENST00000298556.8	NP_000185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPRT1	ENST00000298556.8	c.319-3637T>A		intron_variant		1	NM_000194.3	ENSP00000298556.7
HPRT1	ENST00000462974.5	n.477-3637T>A		intron_variant		3
HPRT1	ENST00000475720.1	n.277-3637T>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.175 AC: 19153 AN: 109360 Hom.: 1591 Cov.: 22 AF XY: 0.160 AC XY: 5103 AN XY: 31904

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

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.000577

Gnomad4 SAS AF: 0.0600

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.169

Alfa AF: 0.164 Hom.: 927

Bravo AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.82

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

LitVar

Other links and lift over

dbSNP: rs1468266; hg19: chrX-133616858;