3-64522245-C-T

Position:

chr3-64522245-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_182920.2(ADAMTS9):c.5734G>A(p.Val1912Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,614,032 control chromosomes in the GnomAD database, including 2 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 2 hom. )

Consequence

ADAMTS9
NM_182920.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.23

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011214286).

BP6

Variant 3-64522245-C-T is Benign according to our data. Variant chr3-64522245-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1546394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADAMTS9	NM_182920.2 linkuse as main transcript	c.5734G>A	p.Val1912Ile	missense_variant	39/40	ENST00000498707.5	NP_891550.1
ADAMTS9	NM_001318781.2 linkuse as main transcript	c.5650G>A	p.Val1884Ile	missense_variant	38/39		NP_001305710.1
ADAMTS9	XR_007095711.1 linkuse as main transcript	n.5993G>A		non_coding_transcript_exon_variant	38/40
ADAMTS9	XR_245151.1 linkuse as main transcript	n.6077G>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.5734G>A	p.Val1912Ile	missense_variant	39/40	1	NM_182920.2	ENSP00000418735	P1	Q9P2N4-3

Frequencies

GnomAD3 genomes

AF:

0.00231

AC:

352

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00583

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00241

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00196

AC:

493

AN:

251348

Hom.:

AF XY:

0.00198

AC XY:

269

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00283

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00531

Gnomad NFE exome

AF:

0.00266

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.00200

AC:

2920

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

1445

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00350

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00491

Gnomad4 NFE exome

AF:

0.00218

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00232

AC:

353

AN:

152360

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00272

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00583

Gnomad4 NFE

AF:

0.00243

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00202

Hom.:

Bravo

AF:

0.00192

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00203

AC:

247

EpiCase

AF:

0.00224

EpiControl

AF:

0.00314

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 27, 2023	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

ADAMTS9-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 09, 2019

This variant is classified as likely 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

0.056

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.21

DANN

Benign

0.61

DEOGEN2

Benign

0.052

T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0083

LIST_S2

Benign

0.035

T;T

M_CAP

Benign

0.0094

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.050

N;N

REVEL

Benign

0.052

Sift

Benign

0.72

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.0

B;.

Vest4

0.075

MVP

0.13

MPC

0.15

ClinPred

0.0053

GERP RS

-10

Varity_R

0.036

gMVP

0.11

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