rs387906428

chrX-134500062-AAAATACAAAGCCTAAGATGAG-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_000194.3(HPRT1):c.644_*7del variant causes a stop lost, 3 prime UTR change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic,other (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: HPRT1 NM_000194.3 stop_lost, 3_prime_UTR
• Clinical Significance: Pathogenic; other no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 8.52

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant X-134500062-AAAATACAAAGCCTAAGATGAG-A is Pathogenic according to our data. Variant chrX-134500062-AAAATACAAAGCCTAAGATGAG-A is described in ClinVar as [Pathogenic, other]. Clinvar id is 10035.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPRT1	NM_000194.3	c.644_*7del		stop_lost, 3_prime_UTR_variant	9/9	ENST00000298556.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPRT1	ENST00000298556.8	c.644_*7del		stop_lost, 3_prime_UTR_variant	9/9	1	NM_000194.3	P1
HPRT1	ENST00000475720.1	n.567+1380_567+1400del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 23

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

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic; other

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Lesch-Nyhan syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 1990

- -

HPRT EVANSVILLE Other:1

other, no assertion criteria provided

literature only

OMIM

Sep 26, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs387906428; hg19: chrX-133634092;