Variant 17-82433808-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001330542.2(HEXD):c.433A>G(p.Ile145Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,611,518 control chromosomes in the GnomAD database, including 126,366 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.43 ( 15296 hom., cov: 33)

Exomes 𝑓: 0.37 ( 111070 hom. )

Consequence

HEXD
NM_001330542.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0800

Variant links:

Genes affected

HEXD (HGNC:26307): (hexosaminidase D) Enables beta-N-acetylhexosaminidase activity. Predicted to be involved in carbohydrate metabolic process. Located in extracellular vesicle. [provided by Alliance of Genome Resources, Apr 2022]

HEXD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.8481857E-6).

BP6

Variant 17-82433808-A-G is Benign according to our data. Variant chr17-82433808-A-G is described in ClinVar as [Benign]. Clinvar id is 402933.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEXD	NM_001330542.2 linkuse as main transcript	c.433A>G	p.Ile145Val	missense_variant	5/13	ENST00000327949.15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEXD	ENST00000327949.15 linkuse as main transcript	c.433A>G	p.Ile145Val	missense_variant	5/13	1	NM_001330542.2	P1	Q8WVB3-1

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

65123

AN:

152064

Hom.:

15255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.453

Gnomad AMR

AF:

0.564

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.909

Gnomad SAS

AF:

0.440

Gnomad FIN

AF:

0.326

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.337

Gnomad OTH

AF:

0.454

GnomAD3 exomes

AF:

0.450

AC:

110502

AN:

245678

Hom.:

28939

AF XY:

0.434

AC XY:

58025

AN XY:

133788

show subpopulations

Gnomad AFR exome

AF:

0.499

Gnomad AMR exome

AF:

0.679

Gnomad ASJ exome

AF:

0.383

Gnomad EAS exome

AF:

0.915

Gnomad SAS exome

AF:

0.432

Gnomad FIN exome

AF:

0.320

Gnomad NFE exome

AF:

0.336

Gnomad OTH exome

AF:

0.421

GnomAD4 exome

AF:

0.372

AC:

542627

AN:

1459336

Hom.:

111070

Cov.:

AF XY:

0.371

AC XY:

269402

AN XY:

725982

show subpopulations

Gnomad4 AFR exome

AF:

0.503

Gnomad4 AMR exome

AF:

0.662

Gnomad4 ASJ exome

AF:

0.381

Gnomad4 EAS exome

AF:

0.914

Gnomad4 SAS exome

AF:

0.430

Gnomad4 FIN exome

AF:

0.328

Gnomad4 NFE exome

AF:

0.333

Gnomad4 OTH exome

AF:

0.399

GnomAD4 genome

AF:

0.429

AC:

65216

AN:

152182

Hom.:

15296

Cov.:

AF XY:

0.433

AC XY:

32186

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.496

Gnomad4 AMR

AF:

0.565

Gnomad4 ASJ

AF:

0.384

Gnomad4 EAS

AF:

0.909

Gnomad4 SAS

AF:

0.438

Gnomad4 FIN

AF:

0.326

Gnomad4 NFE

AF:

0.337

Gnomad4 OTH

AF:

0.459

Alfa

AF:

0.371

Hom.:

22295

Bravo

AF:

0.455

TwinsUK

AF:

0.326

AC:

1209

ALSPAC

AF:

0.330

AC:

1271

ESP6500AA

AF:

0.474

AC:

1839

ESP6500EA

AF:

0.338

AC:

2796

ExAC

AF:

0.438

AC:

52917

Asia WGS

AF:

0.658

AC:

2285

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.24

Cadd

Benign

0.13

Dann

Benign

0.38

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.62

T;.;T;T;T

MetaRNN

Benign

0.0000048

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

0.99

P;P;P

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.65

N;N;.;.;.

REVEL

Uncertain

0.33

Sift

Benign

0.28

T;T;.;.;.

Sift4G

Benign

0.35

T;T;T;T;.

Vest4

0.18

MPC

0.23

ClinPred

0.0032

GERP RS

0.036

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.38

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