rs6634993

Variant names:

• chrX-134495484-G-A
• rs6634993
• NM_000194.3:c.485+1894G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-134495484-G-A
• chrX-134495484-G-C

Variant summary

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

The NM_000194.3(HPRT1):​c.485+1894G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 111,285 control chromosomes in the GnomAD database, including 1,126 homozygotes. There are 4,585 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 0.15 (1126 hom., 4585 hem., cov: 23)
• Consequence: HPRT1 NM_000194.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPRT1	NM_000194.3	c.485+1894G>A		intron_variant	Intron 6 of 8	ENST00000298556.8	NP_000185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPRT1	ENST00000298556.8	c.485+1894G>A		intron_variant	Intron 6 of 8	1	NM_000194.3	ENSP00000298556.7
HPRT1	ENST00000462974.5	n.643+1894G>A		intron_variant	Intron 6 of 7	3
HPRT1	ENST00000475720.1	n.443+1894G>A		intron_variant	Intron 5 of 7	3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 16279 AN: 111239 Hom.: 1125 Cov.: 23

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0646

Gnomad AMR AF: 0.0997

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.0457

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.0932

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.147 AC: 16312 AN: 111285 Hom.: 1126 Cov.: 23 AF XY: 0.137 AC XY: 4585 AN XY: 33545

African (AFR) AF: 0.254 AC: 7784 AN: 30586

American (AMR) AF: 0.0995 AC: 1037 AN: 10419

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 315 AN: 2638

East Asian (EAS) AF: 0.216 AC: 766 AN: 3539

South Asian (SAS) AF: 0.0474 AC: 127 AN: 2678

European-Finnish (FIN) AF: 0.0895 AC: 529 AN: 5913

Middle Eastern (MID) AF: 0.0930 AC: 20 AN: 215

European-Non Finnish (NFE) AF: 0.103 AC: 5464 AN: 53098

Other (OTH) AF: 0.149 AC: 226 AN: 1518

Alfa AF: 0.124 Hom.: 1392

Bravo AF: 0.155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.2
DANN	Benign	0.89
PhyloP100		-1.0
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: rs6634993; hg19: chrX-133629514;