Variant X-134460315-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM1BP4

The NM_000194.3(HPRT1):c.4G>T(p.Ala2Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000354 in 1,131,098 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.0000020 ( 0 hom. 1 hem. )

Consequence

HPRT1
NM_000194.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM1

In a modified_residue N-acetylalanine (size 0) in uniprot entity HPRT_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.3826848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPRT1	NM_000194.3 link	c.4G>T	p.Ala2Ser	missense_variant	1/9	ENST00000298556.8	NP_000185.1	P00492A0A140VJL3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPRT1	ENST00000298556.8 link	c.4G>T	p.Ala2Ser	missense_variant	1/9	1	NM_000194.3	ENSP00000298556.7		P00492
HPRT1	ENST00000462974.5 link	n.-36G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000177

AC:

AN:

113087

Hom.:

Cov.:

AF XY:

0.0000283

AC XY:

AN XY:

35381

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000185

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000196

AC:

AN:

1018011

Hom.:

Cov.:

AF XY:

0.00000304

AC XY:

AN XY:

329261

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000124

Gnomad4 OTH exome

AF:

0.0000235

GnomAD4 genome

AF:

0.0000177

AC:

AN:

113087

Hom.:

Cov.:

AF XY:

0.0000283

AC XY:

AN XY:

35381

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000185

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.35

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.38

M_CAP

Pathogenic

1.0

MetaRNN

Benign

0.38

MetaSVM

Pathogenic

1.1

MutationAssessor

Benign

1.2

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.13

REVEL

Uncertain

0.31

Sift

Benign

0.47

Sift4G

Benign

0.73

Polyphen

0.0040

Vest4

0.20

MutPred

0.13

Gain of phosphorylation at A2 (P = 0.0267);

MVP

0.69

MPC

1.4

ClinPred

0.15

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over