dbSNP rs4789777: HEXD:c.632-13G>A (chr17-82436654-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001330542.2(HEXD):c.632-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,603,112 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0018 ( 19 hom. )

Consequence

HEXD
NM_001330542.2 intron

Scores

Clinical Significance

Not reported in ClinVar

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BS2

High Homozygotes in GnomAdExome4 at 19 AR gene

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
HEXD	NM_001330542.2	MANE Select	c.632-13G>A	intron	N/A	NP_001317471.1
HEXD	NM_173620.3		c.632-13G>A	intron	N/A	NP_775891.2
HEXD	NM_001369487.1		c.356-13G>A	intron	N/A	NP_001356416.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.00236

AC:

359

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00481

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00419

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.00215

AC:

496

AN:

230950

AF XY:

0.00214

show subpopulations

Gnomad AFR exome

AF:

0.000284

Gnomad AMR exome

AF:

0.000272

Gnomad ASJ exome

AF:

0.00176

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00515

Gnomad NFE exome

AF:

0.00346

Gnomad OTH exome

AF:

0.00264

GnomAD4 exome

AF:

0.00175

AC:

2542

AN:

1450856

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

1349

AN XY:

721256

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33394

American (AMR)

AF:

0.000457

AC:

AN:

43724

Ashkenazi Jewish (ASJ)

AF:

0.00139

AC:

AN:

25956

East Asian (EAS)

AF:

0.00

AC:

AN:

39492

South Asian (SAS)

AF:

0.0000588

AC:

AN:

85012

European-Finnish (FIN)

AF:

0.00529

AC:

260

AN:

49178

Middle Eastern (MID)

AF:

0.000521

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00191

AC:

2115

AN:

1108300

Other (OTH)

AF:

0.00165

AC:

AN:

60042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

112

224

337

449

561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00236

AC:

359

AN:

152256

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

173

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41550

American (AMR)

AF:

0.000523

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00481

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00419

AC:

285

AN:

68010

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00211

Hom.:

3516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.035

(source)

DANN

Benign

0.55

PhyloP100

-0.67

PromoterAI

-0.0051

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(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