Variant 17-82435794-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001330542.2(HEXD):c.553G>A(p.Val185Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,612,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

HEXD
NM_001330542.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3346128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEXD	NM_001330542.2 linkuse as main transcript	c.553G>A	p.Val185Met	missense_variant	6/13	ENST00000327949.15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEXD	ENST00000327949.15 linkuse as main transcript	c.553G>A	p.Val185Met	missense_variant	6/13	1	NM_001330542.2	P1	Q8WVB3-1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000125

AC:

AN:

247072

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

134688

show subpopulations

Gnomad AFR exome

AF:

0.0000660

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000501

Gnomad EAS exome

AF:

0.0000560

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000171

AC:

250

AN:

1460448

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

108

AN XY:

726582

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.000728

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000193

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000164

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000263

Hom.:

Bravo

AF:

0.000181

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.0000911

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000356

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

Apr 07, 2022

The c.553G>A (p.V185M) alteration is located in exon 6 (coding exon 5) of the HEXDC gene. This alteration results from a G to A substitution at nucleotide position 553, causing the valine (V) at amino acid position 185 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

0.18

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Uncertain

0.010

Cadd

Benign

Dann

Benign

0.84

Eigen

Benign

-0.012

Eigen_PC

Benign

-0.068

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.72

T;.;T;T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.33

T;T;T;T;T

MetaSVM

Uncertain

0.78

MutationTaster

Benign

0.85

D;D;D

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-2.1

N;N;.;.;.

REVEL

Uncertain

0.57

Sift

Uncertain

0.013

D;T;.;.;.

Sift4G

Uncertain

0.026

D;T;D;D;.

Vest4

0.66

MVP

0.75

MPC

0.46

ClinPred

0.071

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.55

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