chrX-134473151-A-G

Variant names:

• chrX-134473151-A-G
• rs5933415
• NM_000194.3:c.28-208A>G

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 GnomAd4 at 5 XLR,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPRT1	NM_000194.3	c.28-208A>G		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.28-208A>G		intron_variant	Intron 1 of 8	1	NM_000194.3	ENSP00000298556.7
HPRT1	ENST00000462974.5	n.186-208A>G		intron_variant	Intron 1 of 7	3
HPRT1	ENST00000475720.1	n.-223A>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00703 AC: 785 AN: 111629 Hom.: 5 Cov.: 23

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

African (AFR) AF: 0.000649 AC: 20 AN: 30818

American (AMR) AF: 0.00409 AC: 43 AN: 10524

Ashkenazi Jewish (ASJ) AF: 0.00417 AC: 11 AN: 2636

East Asian (EAS) AF: 0.00 AC: 0 AN: 3564

South Asian (SAS) AF: 0.00488 AC: 13 AN: 2666

European-Finnish (FIN) AF: 0.0339 AC: 203 AN: 5986

Middle Eastern (MID) AF: 0.00922 AC: 2 AN: 217

European-Non Finnish (NFE) AF: 0.00908 AC: 482 AN: 53072

Other (OTH) AF: 0.00661 AC: 10 AN: 1514

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

May 15, 2021

GeneDx

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	-0.91
CADD	Benign	3.0
DANN	Benign	0.76
PhyloP100		-0.27
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

Publications

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Other links and lift over

dbSNP: rs5933415; hg19: chrX-133607181;