X-134473151-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000194.3(HPRT1):c.28-208A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00703 in 111,680 control chromosomes in the GnomAD database, including 5 homozygotes. There are 264 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0070 (5 hom., 264 hem., cov: 23)
• Consequence: HPRT1 NM_000194.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.271

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-134473151-A-G is Benign according to our data. Variant chrX-134473151-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1327201.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPRT1	NM_000194.3	c.28-208A>G		intron_variant		ENST00000298556.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPRT1	ENST00000298556.8	c.28-208A>G		intron_variant		1	NM_000194.3	P1
HPRT1	ENST00000462974.5	n.186-208A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00703 AC: 785 AN: 111629 Hom.: 5 Cov.: 23 AF XY: 0.00781 AC XY: 264 AN XY: 33823

Gnomad AFR AF: 0.000650

Gnomad AMI AF: 0.00146

Gnomad AMR AF: 0.00409

Gnomad ASJ AF: 0.00417

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00486

Gnomad FIN AF: 0.0339

Gnomad MID AF: 0.00840

Gnomad NFE AF: 0.00908

Gnomad OTH AF: 0.00669

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

GnomAD4 genome AF: 0.00703 AC: 785 AN: 111680 Hom.: 5 Cov.: 23 AF XY: 0.00779 AC XY: 264 AN XY: 33884

Gnomad4 AFR AF: 0.000649

Gnomad4 AMR AF: 0.00409

Gnomad4 ASJ AF: 0.00417

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00488

Gnomad4 FIN AF: 0.0339

Gnomad4 NFE AF: 0.00908

Gnomad4 OTH AF: 0.00661

Alfa AF: 0.00821 Hom.: 40

Bravo AF: 0.00506

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.0
Dann	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs5933415; hg19: chrX-133607181;