Variant chr15-72343447-T-C 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.*630A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0531 in 152,994 control chromosomes in the GnomAD database, including 344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 343 hom., cov: 31)

Exomes 𝑓: 0.029 ( 1 hom. )

Consequence

HEXA
NM_000520.6 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.176

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=-0.84).

BP6

Variant 15-72343447-T-C is Benign according to our data. Variant chr15-72343447-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 317032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEXA	NM_000520.6 linkuse as main transcript	c.*630A>G		3_prime_UTR_variant	14/14	ENST00000268097.10	NP_000511.2
HEXA	NM_001318825.2 linkuse as main transcript	c.*630A>G		3_prime_UTR_variant	14/14		NP_001305754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEXA	ENST00000268097.10 linkuse as main transcript	c.*630A>G		3_prime_UTR_variant	14/14	1	NM_000520.6	ENSP00000268097	P1	P06865-1
	ENST00000570175.1 linkuse as main transcript	n.166-1939T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0533

AC:

8091

AN:

151862

Hom.:

345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0793

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.0285

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.0517

Gnomad FIN

AF:

0.0415

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0344

Gnomad OTH

AF:

0.0503

GnomAD4 exome

AF:

0.0286

AC:

AN:

1014

Hom.:

Cov.:

AF XY:

0.0230

AC XY:

AN XY:

522

show subpopulations

Gnomad4 AMR exome

AF:

0.0380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.375

Gnomad4 SAS exome

AF:

0.0556

Gnomad4 NFE exome

AF:

0.0216

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0533

AC:

8096

AN:

151980

Hom.:

343

Cov.:

AF XY:

0.0534

AC XY:

3965

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.0793

Gnomad4 AMR

AF:

0.0284

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.214

Gnomad4 SAS

AF:

0.0522

Gnomad4 FIN

AF:

0.0415

Gnomad4 NFE

AF:

0.0344

Gnomad4 OTH

AF:

0.0498

Alfa

AF:

0.0537

Hom.:

Bravo

AF:

0.0530

Asia WGS

AF:

0.118

AC:

408

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Tay-Sachs disease

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.1

DANN

Benign

0.43

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