X-134498412-CGA-AGG

Variant names:

• chrX-134498412-CGA-AGG
• NM_000194.3:c.508_510delCGAinsAGG
• HPRT1 p.171

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000194.3(HPRT1):​c.508_510delCGAinsAGG​(p.171) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R170R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: HPRT1 NM_000194.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.23
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.508_510delCGAinsAGG	p.171	synonymous	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.508_510delCGAinsAGG	p.171	synonymous	N/A	ENSP00000298556.7	P00492
	HPRT1	ENST00000969780.1		c.553_555delCGAinsAGG	p.186	synonymous	N/A	ENSP00000639839.1
	HPRT1	ENST00000969779.1		c.544_546delCGAinsAGG	p.183	synonymous	N/A	ENSP00000639838.1

Frequencies

GnomAD3 genomes Cov.: 23

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-133632442;