rs17070967

Positions:

chr3-64541599-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182920.2(ADAMTS9):c.5219A>G(p.Lys1740Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00802 in 1,614,014 control chromosomes in the GnomAD database, including 502 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0099 ( 51 hom., cov: 32)

Exomes 𝑓: 0.0078 ( 451 hom. )

Consequence

ADAMTS9
NM_182920.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.18

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 links:

ADAMTS9 (HGNC:):

ADAMTS9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030217767).

BP6

Variant 3-64541599-T-C is Benign according to our data. Variant chr3-64541599-T-C is described in ClinVar as [Benign]. Clinvar id is 1251224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.071 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS9	NM_182920.2 linkuse as main transcript	c.5219A>G	p.Lys1740Arg	missense_variant	34/40	ENST00000498707.5	NP_891550.1	Q9P2N4-3
ADAMTS9	NM_001318781.2 linkuse as main transcript	c.5135A>G	p.Lys1712Arg	missense_variant	33/39		NP_001305710.1	Q9P2N4-4
ADAMTS9	XR_007095711.1 linkuse as main transcript	n.5478A>G		non_coding_transcript_exon_variant	33/40
ADAMTS9	XR_245151.1 linkuse as main transcript	n.5562A>G		non_coding_transcript_exon_variant	34/41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADAMTS9	ENST00000498707.5 linkuse as main transcript	c.5219A>G	p.Lys1740Arg	missense_variant	34/40	1	NM_182920.2	ENSP00000418735.1	Q9P2N4-3
ADAMTS9	ENST00000295903.8 linkuse as main transcript	c.5135A>G	p.Lys1712Arg	missense_variant	33/39	1		ENSP00000295903.4	Q9P2N4-4
ADAMTS9	ENST00000481060.2 linkuse as main transcript	c.2384A>G	p.Lys795Arg	missense_variant	15/21	2		ENSP00000417521.1	H0Y859

Frequencies

GnomAD3 genomes

AF:

0.00983

AC:

1496

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0446

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.0769

Gnomad SAS

AF:

0.0356

Gnomad FIN

AF:

0.00499

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.0138

GnomAD3 exomes

AF:

0.0233

AC:

5855

AN:

250830

Hom.:

278

AF XY:

0.0209

AC XY:

2838

AN XY:

135646

show subpopulations

Gnomad AFR exome

AF:

0.00174

Gnomad AMR exome

AF:

0.0941

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.0763

Gnomad SAS exome

AF:

0.0284

Gnomad FIN exome

AF:

0.00351

Gnomad NFE exome

AF:

0.000926

Gnomad OTH exome

AF:

0.0147

GnomAD4 exome

AF:

0.00782

AC:

11433

AN:

1461760

Hom.:

451

Cov.:

AF XY:

0.00810

AC XY:

5888

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.0914

Gnomad4 ASJ exome

AF:

0.00272

Gnomad4 EAS exome

AF:

0.0835

Gnomad4 SAS exome

AF:

0.0295

Gnomad4 FIN exome

AF:

0.00313

Gnomad4 NFE exome

AF:

0.000593

Gnomad4 OTH exome

AF:

0.00881

GnomAD4 genome

AF:

0.00991

AC:

1509

AN:

152254

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

870

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00248

Gnomad4 AMR

AF:

0.0452

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.0773

Gnomad4 SAS

AF:

0.0361

Gnomad4 FIN

AF:

0.00499

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00639

Hom.:

Bravo

AF:

0.0141

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.0204

AC:

2476

Asia WGS

AF:

0.0510

AC:

177

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

ADAMTS9-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 12, 2019

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

0.067

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.063

T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.67

T;T

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.024

Sift

Benign

0.24

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.0060

B;.

Vest4

0.068

MPC

0.16

ClinPred

0.0031

GERP RS

3.4

Varity_R

0.057

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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