Variant 17-82435791-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001330542.2(HEXD):c.550G>A(p.Gly184Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000504 in 1,612,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 0 hom. )

Consequence

HEXD
NM_001330542.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.824

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038673192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEXD	NM_001330542.2 linkuse as main transcript	c.550G>A	p.Gly184Ser	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.550G>A	p.Gly184Ser	missense_variant	6/13	1	NM_001330542.2	P1	Q8WVB3-1

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000344

AC:

AN:

247280

Hom.:

AF XY:

0.000371

AC XY:

AN XY:

134756

show subpopulations

Gnomad AFR exome

AF:

0.000197

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000680

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000516

AC:

754

AN:

1460484

Hom.:

Cov.:

AF XY:

0.000502

AC XY:

365

AN XY:

726596

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000421

Gnomad4 NFE exome

AF:

0.000638

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000381

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000658

Hom.:

Bravo

AF:

0.000317

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000600

AC:

ExAC

AF:

0.000298

AC:

EpiCase

AF:

0.000763

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.550G>A (p.G184S) 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 550, causing the glycine (G) at amino acid position 184 to be replaced by a serine (S). 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

0.077

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.14

Cadd

Benign

9.2

Dann

Benign

0.92

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.22

T;.;T;T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.039

T;T;T;T;T

MetaSVM

Benign

-0.41

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.91

N;N;.;.;.

REVEL

Benign

0.23

Sift

Benign

0.40

T;T;.;.;.

Sift4G

Benign

0.35

T;T;T;T;.

Vest4

0.35

MVP

0.41

MPC

0.18

ClinPred

0.0082

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.64

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