dbSNP rs748658007: HPRT1:c.384+9C>T (chrX-134486539-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_000194.3(HPRT1):c.384+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000019 ( 0 hom., 0 hem., cov: 20)

Exomes 𝑓: 0.000040 ( 0 hom. 11 hem. )

Consequence

HPRT1
NM_000194.3 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.45

Publications

0 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: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant X-134486539-C-T is Benign according to our data. Variant chrX-134486539-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 435446.

BS2

High Hemizygotes in GnomAdExome4 at 11 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPRT1	NM_000194.3 link	c.384+9C>T		intron_variant	Intron 4 of 8	ENST00000298556.8	NP_000185.1	P00492A0A140VJL3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HPRT1	ENST00000298556.8 link	c.384+9C>T	intron_variant	Intron 4 of 8	1	NM_000194.3	ENSP00000298556.7	P00492
HPRT1	ENST00000462974.5 link	n.542+9C>T	intron_variant	Intron 4 of 7	3
HPRT1	ENST00000475720.1 link	n.342+9C>T	intron_variant	Intron 3 of 7	3

Frequencies

GnomAD3 genomes

AF:

0.0000189

AC:

AN:

105897

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000387

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000396

AC:

AN:

176564

AF XY:

0.0000648

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000736

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000771

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000402

AC:

AN:

970142

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

272848

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23971

American (AMR)

AF:

0.00

AC:

AN:

34649

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18266

East Asian (EAS)

AF:

0.0000343

AC:

AN:

29164

South Asian (SAS)

AF:

0.00

AC:

AN:

50745

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3765

European-Non Finnish (NFE)

AF:

0.0000494

AC:

AN:

728374

Other (OTH)

AF:

0.0000481

AC:

AN:

41616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000189

AC:

AN:

105897

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

29325

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29101

American (AMR)

AF:

0.00

AC:

AN:

9704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2597

East Asian (EAS)

AF:

0.00

AC:

AN:

3416

South Asian (SAS)

AF:

0.00

AC:

AN:

2431

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4585

Middle Eastern (MID)

AF:

0.00

AC:

AN:

229

European-Non Finnish (NFE)

AF:

0.0000387

AC:

AN:

51742

Other (OTH)

AF:

0.00

AC:

AN:

1417

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000843

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 25, 2016

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Lesch-Nyhan syndrome;C0268117:Partial hypoxanthine-guanine phosphoribosyltransferase deficiency

Benign:1

Jan 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: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

-0.51

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism

(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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over