HEXA p.Arg510*

Variant names:

• chr15-72344045-CT-TA
• NM_000520.6:c.*31_*32delAGinsTA

Your query was ambiguous. Multiple possible variants found:

• chr15-72344045-CT-TA
• chr15-72346585-ACG-TTA
• chr15-72346053-ACG-TTA
• chr15-72345475-ACG-TTA
• chr15-72345460-GCG-TTA
• chr15-72346585-ACG-TCA
• chr15-72346053-ACG-TCA
• chr15-72345475-ACG-TCA
• chr15-72345460-GCG-TCA
• chr15-72346585-ACG-CTA
• chr15-72346053-ACG-CTA
• chr15-72345475-ACG-CTA
• chr15-72345460-GCG-CTA
• chr15-72344139-G-A

Variant summary

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

The NM_000520.6(HEXA):​c.*31_*32delAGinsTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HEXA NM_000520.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466
• Publications: 0 publications found

Genes affected

HEXA (HGNC:4878): (hexosaminidase subunit alpha) This gene encodes a member of the glycosyl hydrolase 20 family of proteins. The encoded preproprotein is proteolytically processed to generate the alpha subunit of the lysosomal enzyme beta-hexosaminidase. This enzyme, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Mutations in this gene lead to an accumulation of GM2 ganglioside in neurons, the underlying cause of neurodegenerative disorders termed the GM2 gangliosidoses, including Tay-Sachs disease (GM2-gangliosidosis type I). Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

HEXA Gene-Disease associations (from GenCC):

• Tay-Sachs disease

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Myriad Women's Health, ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000260729 (HGNC:):

CELF6-AS1 (HGNC:58304):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000520.6. 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
	HEXA	NM_000520.6	MANE Select	c.*31_*32delAGinsTA		3_prime_UTR	Exon 14 of 14	NP_000511.2	P06865-1
	HEXA	NM_001318825.2		c.*31_*32delAGinsTA		3_prime_UTR	Exon 14 of 14	NP_001305754.1	H3BP20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEXA	ENST00000268097.10	TSL:1 MANE Select	c.*31_*32delAGinsTA		3_prime_UTR	Exon 14 of 14	ENSP00000268097.6	P06865-1
	ENSG00000260729	ENST00000379915.4	TSL:2	n.608+1400_608+1401delAGinsTA		intron	N/A	ENSP00000478716.1	A0A087WUJ7
	CELF6-AS1	ENST00000570175.1	TSL:1	n.166-1341_166-1340delCTinsTA		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.47

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: chr15-72636386;