NM_000520.6:c.806-48G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000520.6(HEXA):c.806-48G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,417,158 control chromosomes in the GnomAD database, including 1,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 690 hom., cov: 32)

Exomes 𝑓: 0.010 ( 781 hom. )

Consequence

HEXA
NM_000520.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.142

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

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

HEXA links:

ENSG00000260729 (HGNC:):

ENSG00000260729 links:

ENSG00000261460 (HGNC:58304):

ENSG00000261460 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 15-72349307-C-A is Benign according to our data. Variant chr15-72349307-C-A is described in ClinVar as Benign. ClinVar VariationId is 256353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
HEXA	NM_000520.6 link	c.806-48G>T	intron_variant	Intron 7 of 13	ENST00000268097.10	NP_000511.2
HEXA	NM_001318825.2 link	c.839-48G>T	intron_variant	Intron 7 of 13		NP_001305754.1
HEXA	NR_134869.3 link	n.848-48G>T	intron_variant	Intron 7 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEXA	ENST00000268097.10 link	c.806-48G>T		intron_variant	Intron 7 of 13	1	NM_000520.6	ENSP00000268097.6
ENSG00000260729	ENST00000379915.4 link	n.413-2982G>T		intron_variant	Intron 3 of 15	2		ENSP00000478716.1

Frequencies

GnomAD3 genomes

AF:

0.0563

AC:

8572

AN:

152148

Hom.:

685

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0706

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00253

Gnomad OTH

AF:

0.0492

GnomAD2 exomes

AF:

0.0268

AC:

6640

AN:

247350

AF XY:

0.0204

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.0965

Gnomad ASJ exome

AF:

0.00151

Gnomad EAS exome

AF:

0.000873

Gnomad FIN exome

AF:

0.000282

Gnomad NFE exome

AF:

0.00242

Gnomad OTH exome

AF:

0.0182

GnomAD4 exome

AF:

0.0103

AC:

13022

AN:

1264892

Hom.:

781

Cov.:

AF XY:

0.00906

AC XY:

5798

AN XY:

639894

show subpopulations

African (AFR)

AF:

0.181

AC:

5338

AN:

29530

American (AMR)

AF:

0.0938

AC:

4165

AN:

44424

Ashkenazi Jewish (ASJ)

AF:

0.00156

AC:

AN:

24934

East Asian (EAS)

AF:

0.000464

AC:

AN:

38758

South Asian (SAS)

AF:

0.00317

AC:

261

AN:

82266

European-Finnish (FIN)

AF:

0.000228

AC:

AN:

52744

Middle Eastern (MID)

AF:

0.0142

AC:

AN:

4436

European-Non Finnish (NFE)

AF:

0.00237

AC:

2213

AN:

934056

Other (OTH)

AF:

0.0170

AC:

913

AN:

53744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

659

1317

1976

2634

3293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

244

488

732

976

1220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0565

AC:

8607

AN:

152266

Hom.:

690

Cov.:

AF XY:

0.0555

AC XY:

4134

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.174

AC:

7210

AN:

41530

American (AMR)

AF:

0.0710

AC:

1087

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5190

South Asian (SAS)

AF:

0.00311

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00253

AC:

172

AN:

68022

Other (OTH)

AF:

0.0530

AC:

112

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

370

740

1111

1481

1851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0243

Hom.:

Bravo

AF:

0.0679

Asia WGS

AF:

0.0240

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 20, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Tay-Sachs disease

Benign:1

Apr 12, 2018

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.5

(source)

DANN

Benign

0.55

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over