rs137852494

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PM1PM2PP2PP3_StrongPP5

The NM_000194.3(HPRT1):c.151C>G(p.Arg51Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic,other (no stars).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

HPRT1
NM_000194.3 missense

Scores

Clinical Significance

Pathogenic; other no assertion criteria provided P:1O:1

Conservation

PhyloP100: 3.75

Publications

19 publications found

Variant links:

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]

HPRT1 Gene-Disease associations (from GenCC):

Lesch-Nyhan syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
hypoxanthine guanine phosphoribosyltransferase partial deficiency
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

HPRT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 ACMG points.

PM1

In a hotspot region, there are 7 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_000194.3

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 31 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: 2.3178 (below the threshold of 3.09). Trascript score misZ: NaN (below the threshold of 3.09). GenCC associations: The gene is linked to Lesch-Nyhan syndrome, hypoxanthine guanine phosphoribosyltransferase partial deficiency.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.981

PP5

Variant X-134475197-C-G is Pathogenic according to our data. Variant chrX-134475197-C-G is described in ClinVar as [Pathogenic, other]. Clinvar id is 10059.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPRT1	NM_000194.3 link	c.151C>G	p.Arg51Gly	missense_variant	Exon 3 of 9	ENST00000298556.8	NP_000185.1	P00492A0A140VJL3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HPRT1	ENST00000298556.8 link	c.151C>G	p.Arg51Gly	missense_variant	Exon 3 of 9	1	NM_000194.3	ENSP00000298556.7	P00492
HPRT1	ENST00000462974.5 link	n.309C>G		non_coding_transcript_exon_variant	Exon 3 of 8	3
HPRT1	ENST00000475720.1 link	n.109C>G		non_coding_transcript_exon_variant	Exon 2 of 8	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1090654

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

356592

African (AFR)

AF:

0.00

AC:

AN:

26241

American (AMR)

AF:

0.00

AC:

AN:

35200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19329

East Asian (EAS)

AF:

0.00

AC:

AN:

30178

South Asian (SAS)

AF:

0.00

AC:

AN:

53978

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4107

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

835258

Other (OTH)

AF:

0.00

AC:

AN:

45849

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic; other

Submissions summary: Pathogenic:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Partial hypoxanthine-guanine phosphoribosyltransferase deficiency

Pathogenic:1

Sep 01, 1983

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

HPRT TORONTO

Other:1

Sep 10, 2020

OMIM

Significance:other

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Pathogenic

0.59

BayesDel_noAF

Pathogenic

0.61

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.97

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.78

MetaRNN

Pathogenic

0.98

MetaSVM

Pathogenic

1.2

MutationAssessor

Uncertain

2.1

PhyloP100

3.7

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-4.5

REVEL

Pathogenic

0.80

Sift

Uncertain

0.017

Sift4G

Benign

0.17

Polyphen

0.081

Vest4

0.94

MutPred

0.84

Loss of stability (P = 0.0244);

MVP

1.0

MPC

2.0

ClinPred

0.99

GERP RS

4.7

Varity_R

0.88

gMVP

0.97

Mutation Taster

=15/85

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over