X-134465599-C-T

Variant names:

• chrX-134465599-C-T
• rs6638241
• NM_000194.3:c.27+5261C>T

Variant summary

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

The NM_000194.3(HPRT1):​c.27+5261C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 112,024 control chromosomes in the GnomAD database, including 828 homozygotes. There are 4,215 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 0.13 (828 hom., 4215 hem., cov: 23)
• Consequence: HPRT1 NM_000194.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286
• 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: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
• hypoxanthine guanine phosphoribosyltransferase partial deficiency

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPRT1	NM_000194.3	c.27+5261C>T		intron_variant	Intron 1 of 8	ENST00000298556.8	NP_000185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPRT1	ENST00000298556.8	c.27+5261C>T		intron_variant	Intron 1 of 8	1	NM_000194.3	ENSP00000298556.7
HPRT1	ENST00000462974.5	n.185+5064C>T		intron_variant	Intron 1 of 7	3

Frequencies

GnomAD3 genomes AF: 0.131 AC: 14635 AN: 111971 Hom.: 826 Cov.: 23

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0634

Gnomad AMR AF: 0.0943

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.0484

Gnomad FIN AF: 0.0906

Gnomad MID AF: 0.0879

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.131 AC: 14666 AN: 112024 Hom.: 828 Cov.: 23 AF XY: 0.123 AC XY: 4215 AN XY: 34228

African (AFR) AF: 0.200 AC: 6154 AN: 30809

American (AMR) AF: 0.0941 AC: 994 AN: 10559

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 315 AN: 2642

East Asian (EAS) AF: 0.215 AC: 763 AN: 3555

South Asian (SAS) AF: 0.0496 AC: 137 AN: 2760

European-Finnish (FIN) AF: 0.0906 AC: 547 AN: 6037

Middle Eastern (MID) AF: 0.0872 AC: 19 AN: 218

European-Non Finnish (NFE) AF: 0.103 AC: 5489 AN: 53217

Other (OTH) AF: 0.132 AC: 205 AN: 1549

Alfa AF: 0.115 Hom.: 7738

Bravo AF: 0.136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.82
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs6638241; hg19: chrX-133599629;