rs2077615596

Variant names:

• chrX-134473346-A-G
• rs2077615596
• NM_000194.3:c.28-13A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-134473346-A-G
• chrX-134473346-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000194.3(HPRT1):​c.28-13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000114 in 873,409 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000011 (0 hom. 0 hem.)
• Consequence: HPRT1 NM_000194.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0680
• Publications: 0 publications found

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: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics, Orphanet
• hypoxanthine guanine phosphoribosyltransferase partial deficiency

  Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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=-0.57).
• BP6: Variant X-134473346-A-G is Benign according to our data. Variant chrX-134473346-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2939555.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000194.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPRT1	NM_000194.3	MANE Select	c.28-13A>G		intron	N/A	NP_000185.1	A0A140VJL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPRT1	ENST00000298556.8	TSL:1 MANE Select	c.28-13A>G		intron	N/A	ENSP00000298556.7	P00492
	HPRT1	ENST00000969780.1		c.28-13A>G		intron	N/A	ENSP00000639839.1
	HPRT1	ENST00000969779.1		c.28-13A>G		intron	N/A	ENSP00000639838.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000114 AC: 1 AN: 873409 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 250973

African (AFR) AF: 0.00 AC: 0 AN: 22206

American (AMR) AF: 0.00 AC: 0 AN: 34933

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17964

East Asian (EAS) AF: 0.00 AC: 0 AN: 29092

South Asian (SAS) AF: 0.00 AC: 0 AN: 49517

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3660

European-Non Finnish (NFE) AF: 0.00000157 AC: 1 AN: 637247

Other (OTH) AF: 0.00 AC: 0 AN: 38452

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Lesch-Nyhan syndrome;C0268117:Partial hypoxanthine-guanine phosphoribosyltransferase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.93
PhyloP100		0.068
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2077615596; hg19: chrX-133607376;