chr3-64522181-C-T

Position:

chr3-64522181-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 0.010 ( 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

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:

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=0.0020031333).

BP6

Variant 3-64522181-C-T is Benign according to our data. Variant chr3-64522181-C-T is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	Protein
ADAMTS9	NM_182920.2 linkuse as main transcript	c.5798G>A	p.Arg1933Gln	missense_variant	39/40	ENST00000498707.5	NP_891550.1
ADAMTS9	NM_001318781.2 linkuse as main transcript	c.5714G>A	p.Arg1905Gln	missense_variant	38/39		NP_001305710.1
ADAMTS9	XR_007095711.1 linkuse as main transcript	n.6057G>A		non_coding_transcript_exon_variant	38/40
ADAMTS9	XR_245151.1 linkuse as main transcript	n.6141G>A		non_coding_transcript_exon_variant	39/41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS9	ENST00000498707.5 linkuse as main transcript	c.5798G>A	p.Arg1933Gln	missense_variant	39/40	1	NM_182920.2	ENSP00000418735	P1	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

GnomAD3 exomes

AF:

0.0226

AC:

5667

AN:

251268

Hom.:

258

AF XY:

0.0202

AC XY:

2738

AN XY:

135800

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 SAS exome

AF:

0.0281

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

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.0933

Gnomad4 ASJ exome

AF:

0.00279

Gnomad4 EAS exome

AF:

0.0750

Gnomad4 SAS exome

AF:

0.0291

Gnomad4 FIN exome

AF:

0.00350

Gnomad4 NFE exome

AF:

0.000681

Gnomad4 OTH exome

AF:

0.00864

GnomAD4 genome

AF:

0.0101

AC:

1543

AN:

152328

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

892

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.0495

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.0673

Gnomad4 SAS

AF:

0.0365

Gnomad4 FIN

AF:

0.00555

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00631

Hom.:

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	- -

ADAMTS9-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 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

0.062

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.66

CADD

Benign

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;.

MutationTaster

Benign

0.95

N;N

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

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

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