dbSNP rs4789777: HEXD:c.632-13G>T (chr17-82436654-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001330542.2(HEXD):c.632-13G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,600,844 control chromosomes in the GnomAD database, including 105,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10895 hom., cov: 34)

Exomes 𝑓: 0.34 ( 94439 hom. )

Consequence

HEXD
NM_001330542.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.674

Publications

22 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 17-82436654-G-T is Benign according to our data. Variant chr17-82436654-G-T is described in ClinVar as Benign. ClinVar VariationId is 402934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330542.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HEXD	NM_001330542.2	MANE Select	c.632-13G>T	intron	N/A	NP_001317471.1	Q8WVB3-1
HEXD	NM_173620.3		c.632-13G>T	intron	N/A	NP_775891.2	Q8WVB3-2
HEXD	NM_001369487.1		c.356-13G>T	intron	N/A	NP_001356416.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HEXD	ENST00000327949.15	TSL:1 MANE Select	c.632-13G>T	intron	N/A	ENSP00000332634.9	Q8WVB3-1
HEXD	ENST00000337014.10	TSL:1	c.632-13G>T	intron	N/A	ENSP00000337854.6	Q8WVB3-2
HEXD	ENST00000577944.5	TSL:5	c.632-13G>T	intron	N/A	ENSP00000463129.1	J3QKL0

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54405

AN:

152086

Hom.:

10883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.451

Gnomad AMR

AF:

0.501

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.906

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.389

GnomAD2 exomes

AF:

0.417

AC:

96254

AN:

230950

AF XY:

0.405

show subpopulations

Gnomad AFR exome

AF:

0.329

Gnomad AMR exome

AF:

0.614

Gnomad ASJ exome

AF:

0.360

Gnomad EAS exome

AF:

0.914

Gnomad FIN exome

AF:

0.285

Gnomad NFE exome

AF:

0.313

Gnomad OTH exome

AF:

0.391

GnomAD4 exome

AF:

0.341

AC:

494649

AN:

1448640

Hom.:

94439

Cov.:

AF XY:

0.342

AC XY:

246115

AN XY:

720220

show subpopulations

African (AFR)

AF:

0.332

AC:

11057

AN:

33352

American (AMR)

AF:

0.598

AC:

26138

AN:

43688

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

9315

AN:

25940

East Asian (EAS)

AF:

0.913

AC:

36068

AN:

39484

South Asian (SAS)

AF:

0.407

AC:

34542

AN:

84934

European-Finnish (FIN)

AF:

0.292

AC:

14356

AN:

49092

Middle Eastern (MID)

AF:

0.336

AC:

1936

AN:

5758

European-Non Finnish (NFE)

AF:

0.307

AC:

339392

AN:

1106444

Other (OTH)

AF:

0.364

AC:

21845

AN:

59948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

13286

26573

39859

53146

66432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11448

22896

34344

45792

57240

<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:

0.358

AC:

54444

AN:

152204

Hom.:

10895

Cov.:

AF XY:

0.363

AC XY:

27013

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.325

AC:

13517

AN:

41532

American (AMR)

AF:

0.502

AC:

7674

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

1246

AN:

3470

East Asian (EAS)

AF:

0.906

AC:

4689

AN:

5176

South Asian (SAS)

AF:

0.411

AC:

1985

AN:

4830

European-Finnish (FIN)

AF:

0.288

AC:

3056

AN:

10600

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.308

AC:

20933

AN:

67992

Other (OTH)

AF:

0.393

AC:

832

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1756

3513

5269

7026

8782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.308

Hom.:

3516

Bravo

AF:

0.380

Asia WGS

AF:

0.629

AC:

2185

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.018

(source)

DANN

Benign

0.44

PhyloP100

-0.67

PromoterAI

0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over