rs17070905

Variant names:

Variant summary

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

The NM_182920.2(ADAMTS9):c.5798G>A(p.Arg1933Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00793 in 1,613,902 control chromosomes in the GnomAD database, including 485 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 56 hom., cov: 33)

Exomes 𝑓: 0.0077 ( 429 hom. )

Consequence

ADAMTS9
NM_182920.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.558

Publications

13 publications found

Variant links:

Genes affected

ADAMTS9 (HGNC:13202): (ADAM metallopeptidase with thrombospondin type 1 motif 9) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. Members of the ADAMTS family have been implicated in the cleavage of proteoglycans, the control of organ shape during development, and the inhibition of angiogenesis. This gene is localized to chromosome 3p14.3-p14.2, an area known to be lost in hereditary renal tumors. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Jan 2016]

ADAMTS9 Gene-Disease associations (from GenCC):

nephronophthisis 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
ciliopathy
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ADAMTS9 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 (MetaRNN=0.0020031333).

BP6

Variant 3-64522181-C-T is Benign according to our data. Variant chr3-64522181-C-T is described in ClinVar as Benign. ClinVar VariationId is 1294798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS9	NM_182920.2 link	c.5798G>A	p.Arg1933Gln	missense_variant	Exon 39 of 40	ENST00000498707.5	NP_891550.1	Q9P2N4-3
ADAMTS9	NM_001318781.2 link	c.5714G>A	p.Arg1905Gln	missense_variant	Exon 38 of 39		NP_001305710.1	Q9P2N4-4
ADAMTS9	XR_007095711.1 link	n.6057G>A		non_coding_transcript_exon_variant	Exon 38 of 40
ADAMTS9	XR_245151.1 link	n.6141G>A		non_coding_transcript_exon_variant	Exon 39 of 41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS9	ENST00000498707.5 link	c.5798G>A	p.Arg1933Gln	missense_variant	Exon 39 of 40	1	NM_182920.2	ENSP00000418735.1		Q9P2N4-3

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1530

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0488

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.0670

Gnomad SAS

AF:

0.0360

Gnomad FIN

AF:

0.00555

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.0143

GnomAD2 exomes

AF:

0.0226

AC:

5667

AN:

251268

AF XY:

0.0202

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.0964

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.0614

Gnomad FIN exome

AF:

0.00397

Gnomad NFE exome

AF:

0.00109

Gnomad OTH exome

AF:

0.0137

GnomAD4 exome

AF:

0.00770

AC:

11258

AN:

1461574

Hom.:

429

Cov.:

AF XY:

0.00799

AC XY:

5809

AN XY:

727102

show subpopulations

African (AFR)

AF:

0.00143

AC:

AN:

33454

American (AMR)

AF:

0.0933

AC:

4167

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00279

AC:

AN:

26128

East Asian (EAS)

AF:

0.0750

AC:

2978

AN:

39688

South Asian (SAS)

AF:

0.0291

AC:

2510

AN:

86246

European-Finnish (FIN)

AF:

0.00350

AC:

187

AN:

53408

Middle Eastern (MID)

AF:

0.00278

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000681

AC:

757

AN:

1111820

Other (OTH)

AF:

0.00864

AC:

522

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

541

1081

1622

2162

2703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

150

300

450

600

750

<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:

0.0101

AC:

1543

AN:

152328

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

892

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.00250

AC:

104

AN:

41582

American (AMR)

AF:

0.0495

AC:

757

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.0673

AC:

348

AN:

5170

South Asian (SAS)

AF:

0.0365

AC:

176

AN:

4828

European-Finnish (FIN)

AF:

0.00555

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000838

AC:

AN:

68024

Other (OTH)

AF:

0.0137

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

140

210

280

350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00719

Hom.:

105

Bravo

AF:

0.0142

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.0194

AC:

2360

Asia WGS

AF:

0.0510

AC:

176

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ADAMTS9-related disorder

Benign:1

Jun 12, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.037

T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.81

T;T

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.3

N;.

PhyloP100

0.56

PrimateAI

Benign

0.26

PROVEAN

Benign

1.8

N;N

REVEL

Benign

0.046

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.042

MPC

0.22

ClinPred

0.014

GERP RS

0.86

Varity_R

0.054

gMVP

0.17

Mutation Taster

=98/2

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