Genetic Variant HPRT1:c.27+19C>T (chrX-134460357-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000194.3(HPRT1):c.27+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,100,597 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 0.0000088 ( 0 hom., 0 hem., cov: 25)

Exomes 𝑓: 0.0000020 ( 0 hom. 1 hem. )

Consequence

HPRT1
NM_000194.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.73

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant X-134460357-C-T is Benign according to our data. Variant chrX-134460357-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2953449.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPRT1	NM_000194.3 link	c.27+19C>T		intron_variant	Intron 1 of 8	ENST00000298556.8	NP_000185.1	P00492A0A140VJL3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPRT1	ENST00000298556.8 link	c.27+19C>T		intron_variant	Intron 1 of 8	1	NM_000194.3	ENSP00000298556.7		P00492
HPRT1	ENST00000462974.5 link	n.7C>T		non_coding_transcript_exon_variant	Exon 1 of 8	3

Frequencies

GnomAD3 genomes

AF:

0.00000884

AC:

AN:

113182

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:

0.000160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000203

AC:

AN:

987415

Hom.:

Cov.:

AF XY:

0.00000318

AC XY:

AN XY:

314203

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20971

American (AMR)

AF:

0.00

AC:

AN:

23803

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16617

East Asian (EAS)

AF:

0.00

AC:

AN:

21626

South Asian (SAS)

AF:

0.00

AC:

AN:

45833

European-Finnish (FIN)

AF:

0.0000800

AC:

AN:

24986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

789629

Other (OTH)

AF:

0.00

AC:

AN:

41200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000884

AC:

AN:

113182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35480

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31309

American (AMR)

AF:

0.00

AC:

AN:

10823

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2662

East Asian (EAS)

AF:

0.00

AC:

AN:

3551

South Asian (SAS)

AF:

0.00

AC:

AN:

2864

European-Finnish (FIN)

AF:

0.000160

AC:

AN:

6231

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53287

Other (OTH)

AF:

0.00

AC:

AN:

1537

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

Benign:1

Nov 01, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.72

CADD

Benign

4.0

(source)

DANN

Benign

0.89

PhyloP100

-1.7

PromoterAI

-0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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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chrX-134460357-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over