Genetic Variant HEXD:p.Thr5Thr (chr17-82419814-T-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001330542.2(HEXD):c.15T>G(p.Thr5Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,601,768 control chromosomes in the GnomAD database, including 94,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 14706 hom., cov: 32)

Exomes 𝑓: 0.32 ( 79455 hom. )

Consequence

HEXD
NM_001330542.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.20

Publications

33 publications found

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 was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 17-82419814-T-G is Benign according to our data. Variant chr17-82419814-T-G is described in ClinVar as Benign. ClinVar VariationId is 402932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEXD	NM_001330542.2 link	c.15T>G	p.Thr5Thr	synonymous_variant	Exon 2 of 13	ENST00000327949.15	NP_001317471.1	Q8WVB3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEXD	ENST00000327949.15 link	c.15T>G	p.Thr5Thr	synonymous_variant	Exon 2 of 13	1	NM_001330542.2	ENSP00000332634.9		Q8WVB3-1

Frequencies

GnomAD3 genomes

AF:

0.409

AC:

62173

AN:

151956

Hom.:

14663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.622

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.396

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.708

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.300

Gnomad OTH

AF:

0.414

GnomAD2 exomes

AF:

0.356

AC:

88312

AN:

248414

AF XY:

0.341

show subpopulations

Gnomad AFR exome

AF:

0.635

Gnomad AMR exome

AF:

0.420

Gnomad ASJ exome

AF:

0.299

Gnomad EAS exome

AF:

0.700

Gnomad FIN exome

AF:

0.250

Gnomad NFE exome

AF:

0.294

Gnomad OTH exome

AF:

0.329

GnomAD4 exome

AF:

0.317

AC:

460111

AN:

1449692

Hom.:

79455

Cov.:

AF XY:

0.314

AC XY:

226351

AN XY:

721826

show subpopulations

African (AFR)

AF:

0.632

AC:

20933

AN:

33108

American (AMR)

AF:

0.415

AC:

18447

AN:

44498

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

7776

AN:

26032

East Asian (EAS)

AF:

0.713

AC:

28210

AN:

39548

South Asian (SAS)

AF:

0.267

AC:

22970

AN:

85906

European-Finnish (FIN)

AF:

0.254

AC:

13527

AN:

53330

Middle Eastern (MID)

AF:

0.262

AC:

1505

AN:

5742

European-Non Finnish (NFE)

AF:

0.296

AC:

326339

AN:

1101584

Other (OTH)

AF:

0.340

AC:

20404

AN:

59944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

13094

26188

39283

52377

65471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11000

22000

33000

44000

55000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.409

AC:

62265

AN:

152076

Hom.:

14706

Cov.:

AF XY:

0.404

AC XY:

30063

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.623

AC:

25826

AN:

41472

American (AMR)

AF:

0.395

AC:

6038

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

1053

AN:

3466

East Asian (EAS)

AF:

0.708

AC:

3667

AN:

5176

South Asian (SAS)

AF:

0.269

AC:

1295

AN:

4812

European-Finnish (FIN)

AF:

0.247

AC:

2616

AN:

10580

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.300

AC:

20410

AN:

67970

Other (OTH)

AF:

0.415

AC:

878

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1718

3436

5154

6872

8590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.324

Hom.:

10829

Bravo

AF:

0.434

Asia WGS

AF:

0.465

AC:

1615

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.099

(source)

DANN

Benign

0.63

PhyloP100

-2.2

PromoterAI

0.078

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over