Variant 15-72343562-C-T 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.*515G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 162,730 control chromosomes in the GnomAD database, including 52,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 48315 hom., cov: 32)

Exomes 𝑓: 0.89 ( 4258 hom. )

Consequence

HEXA
NM_000520.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0290

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 15-72343562-C-T is Benign according to our data. Variant chr15-72343562-C-T is described in ClinVar as [Benign]. Clinvar id is 317035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEXA	NM_000520.6 linkuse as main transcript	c.*515G>A		3_prime_UTR_variant	14/14	ENST00000268097.10
HEXA	NM_001318825.2 linkuse as main transcript	c.*515G>A		3_prime_UTR_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEXA	ENST00000268097.10 linkuse as main transcript	c.*515G>A		3_prime_UTR_variant	14/14	1	NM_000520.6	P1	P06865-1
	ENST00000570175.1 linkuse as main transcript	n.166-1824C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.745

AC:

113253

AN:

151962

Hom.:

48331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.294

Gnomad AMI

AF:

0.867

Gnomad AMR

AF:

0.844

Gnomad ASJ

AF:

0.982

Gnomad EAS

AF:

0.762

Gnomad SAS

AF:

0.934

Gnomad FIN

AF:

0.909

Gnomad MID

AF:

0.924

Gnomad NFE

AF:

0.941

Gnomad OTH

AF:

0.788

GnomAD4 exome

AF:

0.886

AC:

9436

AN:

10650

Hom.:

4258

Cov.:

AF XY:

0.891

AC XY:

5036

AN XY:

5654

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.847

Gnomad4 ASJ exome

AF:

0.970

Gnomad4 EAS exome

AF:

0.727

Gnomad4 SAS exome

AF:

0.934

Gnomad4 FIN exome

AF:

0.929

Gnomad4 NFE exome

AF:

0.933

Gnomad4 OTH exome

AF:

0.901

GnomAD4 genome

AF:

0.745

AC:

113244

AN:

152080

Hom.:

48315

Cov.:

AF XY:

0.750

AC XY:

55730

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.294

Gnomad4 AMR

AF:

0.843

Gnomad4 ASJ

AF:

0.982

Gnomad4 EAS

AF:

0.762

Gnomad4 SAS

AF:

0.934

Gnomad4 FIN

AF:

0.909

Gnomad4 NFE

AF:

0.941

Gnomad4 OTH

AF:

0.783

Alfa

AF:

0.821

Hom.:

6885

Bravo

AF:

0.719

Asia WGS

AF:

0.795

AC:

2765

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Tay-Sachs disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.2

DANN

Benign

0.41

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