15-72345454-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000520.6(HEXA):c.1518A>G(p.Glu506Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.979 in 1,614,144 control chromosomes in the GnomAD database, including 778,550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 62364 hom., cov: 34)

Exomes 𝑓: 0.99 ( 716186 hom. )

Consequence

HEXA
NM_000520.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:16

Conservation

PhyloP100: -0.293

Variant links:

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 links:

ENSG00000260729 (HGNC:):

ENSG00000260729 links:

ENSG00000261460 (HGNC:58304):

ENSG00000261460 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 15-72345454-T-C is Benign according to our data. Variant chr15-72345454-T-C is described in ClinVar as [Benign]. Clinvar id is 93191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-72345454-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.293 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEXA	NM_000520.6 link	c.1518A>G	p.Glu506Glu	synonymous_variant	Exon 13 of 14	ENST00000268097.10	NP_000511.2	P06865-1A0A0S2Z3W3
HEXA	NM_001318825.2 link	c.1551A>G	p.Glu517Glu	synonymous_variant	Exon 13 of 14		NP_001305754.1	P06865H3BP20B4DVA7
HEXA	NR_134869.3 link	n.1303A>G		non_coding_transcript_exon_variant	Exon 11 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEXA	ENST00000268097.10 link	c.1518A>G	p.Glu506Glu	synonymous_variant	Exon 13 of 14	1	NM_000520.6	ENSP00000268097.6		P06865-1
ENSG00000260729	ENST00000379915.4 link	n.600A>G		non_coding_transcript_exon_variant	Exon 5 of 16	2		ENSP00000478716.1		A0A087WUJ7

Frequencies

GnomAD3 genomes

AF:

0.889

AC:

135239

AN:

152172

Hom.:

62345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.613

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.962

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

0.997

Gnomad MID

AF:

0.978

Gnomad NFE

AF:

0.998

Gnomad OTH

AF:

0.921

GnomAD3 exomes

AF:

0.971

AC:

244012

AN:

251424

Hom.:

119593

AF XY:

0.979

AC XY:

133012

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.605

Gnomad AMR exome

AF:

0.981

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.999

Gnomad FIN exome

AF:

0.998

Gnomad NFE exome

AF:

0.998

Gnomad OTH exome

AF:

0.988

GnomAD4 exome

AF:

0.988

AC:

1444272

AN:

1461854

Hom.:

716186

Cov.:

AF XY:

0.989

AC XY:

719550

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.600

Gnomad4 AMR exome

AF:

0.979

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.999

Gnomad4 FIN exome

AF:

0.998

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.975

GnomAD4 genome

AF:

0.889

AC:

135312

AN:

152290

Hom.:

62364

Cov.:

AF XY:

0.892

AC XY:

66419

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.613

Gnomad4 AMR

AF:

0.962

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

0.997

Gnomad4 NFE

AF:

0.998

Gnomad4 OTH

AF:

0.922

Alfa

AF:

0.961

Hom.:

59319

Bravo

AF:

0.873

Asia WGS

AF:

0.977

AC:

3397

AN:

3478

EpiCase

AF:

0.998

EpiControl

AF:

0.997

ClinVar

Significance: Benign

Submissions summary: Benign:16

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 18, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Tay-Sachs disease

Benign:5

Jun 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 29, 2017

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:5

Nov 26, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 05, 2018

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 18, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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