chrX-134460335-C-G

Variant names:

• chrX-134460335-C-G
• NM_000194.3:c.24C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_000194.3(HPRT1):​c.24C>G​(p.Val8Val) variant causes a synonymous 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: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: HPRT1 NM_000194.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.401

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant X-134460335-C-G is Benign according to our data. Variant chrX-134460335-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2946569.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.401 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPRT1	NM_000194.3	c.24C>G	p.Val8Val	synonymous_variant	Exon 1 of 9	ENST00000298556.8	NP_000185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPRT1	ENST00000298556.8	c.24C>G	p.Val8Val	synonymous_variant	Exon 1 of 9	1	NM_000194.3	ENSP00000298556.7
HPRT1	ENST00000462974.5	n.-16C>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1009585 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 325449

African (AFR) AF: 0.00 AC: 0 AN: 21799

American (AMR) AF: 0.00 AC: 0 AN: 26377

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17289

East Asian (EAS) AF: 0.00 AC: 0 AN: 23354

South Asian (SAS) AF: 0.00 AC: 0 AN: 47752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2961

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 802467

Other (OTH) AF: 0.00 AC: 0 AN: 42166

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

Apr 17, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		-0.40
PromoterAI		-0.18	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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

hg19: chrX-133594365;