Variant rs16956759 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000520.6(HEXA):c.1074-43C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,573,718 control chromosomes in the GnomAD database, including 1,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 686 hom., cov: 32)

Exomes 𝑓: 0.0099 ( 852 hom. )

Consequence

HEXA
NM_000520.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.981

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 15-72347801-G-C is Benign according to our data. Variant chr15-72347801-G-C is described in ClinVar as [Benign]. Clinvar id is 256349.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	MANE
HEXA	NM_000520.6 linkuse as main transcript	c.1074-43C>G	intron_variant	ENST00000268097.10
HEXA	NM_001318825.2 linkuse as main transcript	c.1107-43C>G	intron_variant
HEXA	NR_134869.3 linkuse as main transcript	n.1115+247C>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEXA	ENST00000268097.10 linkuse as main transcript	c.1074-43C>G		intron_variant		1	NM_000520.6	P1	P06865-1
	ENST00000570175.1 linkuse as main transcript	n.1577+1004G>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0563

AC:

8559

AN:

152150

Hom.:

681

Cov.:

show subpopulations

Gnomad AFR

AF:

0.173

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0706

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00253

Gnomad OTH

AF:

0.0488

GnomAD3 exomes

AF:

0.0267

AC:

6709

AN:

250876

Hom.:

441

AF XY:

0.0202

AC XY:

2740

AN XY:

135610

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.0967

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.000871

Gnomad SAS exome

AF:

0.00262

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00241

Gnomad OTH exome

AF:

0.0186

GnomAD4 exome

AF:

0.00992

AC:

14097

AN:

1421450

Hom.:

852

Cov.:

AF XY:

0.00877

AC XY:

6225

AN XY:

709938

show subpopulations

Gnomad4 AFR exome

AF:

0.182

Gnomad4 AMR exome

AF:

0.0942

Gnomad4 ASJ exome

AF:

0.00158

Gnomad4 EAS exome

AF:

0.000506

Gnomad4 SAS exome

AF:

0.00320

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00236

Gnomad4 OTH exome

AF:

0.0167

GnomAD4 genome

AF:

0.0564

AC:

8594

AN:

152268

Hom.:

686

Cov.:

AF XY:

0.0554

AC XY:

4124

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.173

Gnomad4 AMR

AF:

0.0710

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00253

Gnomad4 OTH

AF:

0.0526

Alfa

AF:

0.00801

Hom.:

Bravo

AF:

0.0680

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 03, 2017	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Tay-Sachs disease

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Apr 12, 2018

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.6

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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