X-134460350-G-A

Variant names:

• chrX-134460350-G-A
• rs1392794109
• NM_000194.3:c.27+12G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000194.3(HPRT1):​c.27+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000010 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: HPRT1 NM_000194.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.822

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant X-134460350-G-A is Benign according to our data. Variant chrX-134460350-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2951598.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPRT1	NM_000194.3	c.27+12G>A		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+12G>A		intron_variant	Intron 1 of 8	1	NM_000194.3	ENSP00000298556.7
HPRT1	ENST00000462974.5	n.-1G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000100 AC: 1 AN: 998971 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 321051

African (AFR) AF: 0.00 AC: 0 AN: 21317

American (AMR) AF: 0.00 AC: 0 AN: 24985

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16946

East Asian (EAS) AF: 0.00 AC: 0 AN: 22372

South Asian (SAS) AF: 0.00 AC: 0 AN: 46963

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25185

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2836

European-Non Finnish (NFE) AF: 0.00000126 AC: 1 AN: 796633

Other (OTH) AF: 0.00 AC: 0 AN: 41734

GnomAD4 genome Cov.: 24

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lesch-Nyhan syndrome;C0268117:Partial hypoxanthine-guanine phosphoribosyltransferase deficiency Benign:1

Sep 04, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		0.82
PromoterAI		-0.26	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

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Other links and lift over

dbSNP: rs1392794109; hg19: chrX-133594380;