Variant 17-82433674-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001330542.2(HEXD):c.299C>T(p.Thr100Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000454 in 1,599,472 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00047 ( 1 hom. )

Consequence

HEXD
NM_001330542.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.792

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0698272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEXD	NM_001330542.2 linkuse as main transcript	c.299C>T	p.Thr100Met	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.299C>T	p.Thr100Met	missense_variant	5/13	1	NM_001330542.2	P1	Q8WVB3-1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000334

AC:

AN:

233256

Hom.:

AF XY:

0.000345

AC XY:

AN XY:

127692

show subpopulations

Gnomad AFR exome

AF:

0.0000695

Gnomad AMR exome

AF:

0.0000985

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000888

Gnomad NFE exome

AF:

0.000514

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000471

AC:

682

AN:

1447214

Hom.:

Cov.:

AF XY:

0.000454

AC XY:

327

AN XY:

720034

show subpopulations

Gnomad4 AFR exome

AF:

0.0000930

Gnomad4 AMR exome

AF:

0.0000242

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000932

Gnomad4 NFE exome

AF:

0.000547

Gnomad4 OTH exome

AF:

0.000351

GnomAD4 genome

AF:

0.000289

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000365

Hom.:

Bravo

AF:

0.000242

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000255

AC:

ESP6500EA

AF:

0.000605

AC:

ExAC

AF:

0.000314

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2022

The c.299C>T (p.T100M) alteration is located in exon 5 (coding exon 4) of the HEXDC gene. This alteration results from a C to T substitution at nucleotide position 299, causing the threonine (T) at amino acid position 100 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.20

Cadd

Benign

Dann

Benign

0.61

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.81

T;.;T;T;T;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.070

T;T;T;T;T;T

MetaSVM

Uncertain

-0.14

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.86

N;N;.;.;.;.

REVEL

Uncertain

0.37

Sift

Benign

0.088

T;T;.;.;.;.

Sift4G

Benign

0.095

T;T;T;T;.;T

Vest4

0.17

MVP

0.53

MPC

0.22

ClinPred

0.030

GERP RS

0.94

gMVP

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