NM_000194.3:c.27+2432T>C

Variant names:

• chrX-134462770-T-C
• rs6638240
• NM_000194.3:c.27+2432T>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.27+2432T>C 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 112,115 control chromosomes in the GnomAD database, including 1,155 homozygotes. There are 4,676 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 (1155 hom., 4676 hem., cov: 23)
• Consequence: HPRT1 NM_000194.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.677
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPRT1	NM_000194.3	c.27+2432T>C		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+2432T>C		intron_variant	Intron 1 of 8	1	NM_000194.3	ENSP00000298556.7
HPRT1	ENST00000462974.5	n.185+2235T>C		intron_variant	Intron 1 of 7	3

Frequencies

GnomAD3 genomes AF: 0.147 AC: 16492 AN: 112058 Hom.: 1154 Cov.: 23

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.0632

Gnomad AMR AF: 0.0990

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.0480

Gnomad FIN AF: 0.0907

Gnomad MID AF: 0.0966

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.147 AC: 16528 AN: 112115 Hom.: 1155 Cov.: 23 AF XY: 0.136 AC XY: 4676 AN XY: 34307

African (AFR) AF: 0.258 AC: 7966 AN: 30842

American (AMR) AF: 0.0988 AC: 1040 AN: 10523

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 316 AN: 2645

East Asian (EAS) AF: 0.210 AC: 748 AN: 3563

South Asian (SAS) AF: 0.0495 AC: 137 AN: 2765

European-Finnish (FIN) AF: 0.0907 AC: 555 AN: 6120

Middle Eastern (MID) AF: 0.0963 AC: 21 AN: 218

European-Non Finnish (NFE) AF: 0.103 AC: 5476 AN: 53228

Other (OTH) AF: 0.148 AC: 226 AN: 1531

Alfa AF: 0.122 Hom.: 1174

Bravo AF: 0.156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	11
DANN	Benign	0.70
PhyloP100		0.68
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: rs6638240; hg19: chrX-133596800;