rs2573652

Positions:

Variant summary

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

The NM_139057.4(ADAMTS17):c.3281A>G(p.Asn1094Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 1,613,878 control chromosomes in the GnomAD database, including 362,029 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 37672 hom., cov: 33)

Exomes 𝑓: 0.66 ( 324357 hom. )

Consequence

ADAMTS17
NM_139057.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.56

Variant links:

Genes affected

ADAMTS17 (HGNC:17109): (ADAM metallopeptidase with thrombospondin type 1 motif 17) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS family members 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. The encoded preproprotein is proteolytically processed to generate the mature protein, which may promote breast cancer cell growth and survival. Mutations in this gene are associated with a Weill-Marchesani-like syndrome, which is characterized by lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature. [provided by RefSeq, May 2016]

ADAMTS17 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=8.221907E-7).

BP6

Variant 15-99974409-T-C is Benign according to our data. Variant chr15-99974409-T-C is described in ClinVar as [Benign]. Clinvar id is 315248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-99974409-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS17	NM_139057.4 linkuse as main transcript	c.3281A>G	p.Asn1094Ser	missense_variant	22/22	ENST00000268070.9	NP_620688.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS17	ENST00000268070.9 linkuse as main transcript	c.3281A>G	p.Asn1094Ser	missense_variant	22/22	1	NM_139057.4	ENSP00000268070		Q8TE56-1
ADAMTS17	ENST00000568565.2 linkuse as main transcript	c.3362A>G	p.Asn1121Ser	missense_variant	23/23	5		ENSP00000456161	P1
ADAMTS17	ENST00000557896.1 linkuse as main transcript	n.389A>G		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.699

AC:

106268

AN:

151998

Hom.:

37633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.809

Gnomad AMI

AF:

0.688

Gnomad AMR

AF:

0.609

Gnomad ASJ

AF:

0.644

Gnomad EAS

AF:

0.557

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.749

Gnomad MID

AF:

0.564

Gnomad NFE

AF:

0.662

Gnomad OTH

AF:

0.650

GnomAD3 exomes

AF:

0.657

AC:

165241

AN:

251370

Hom.:

55178

AF XY:

0.658

AC XY:

89398

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.815

Gnomad AMR exome

AF:

0.548

Gnomad ASJ exome

AF:

0.637

Gnomad EAS exome

AF:

0.564

Gnomad SAS exome

AF:

0.667

Gnomad FIN exome

AF:

0.750

Gnomad NFE exome

AF:

0.665

Gnomad OTH exome

AF:

0.648

GnomAD4 exome

AF:

0.664

AC:

970881

AN:

1461762

Hom.:

324357

Cov.:

AF XY:

0.664

AC XY:

482838

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.814

Gnomad4 AMR exome

AF:

0.558

Gnomad4 ASJ exome

AF:

0.643

Gnomad4 EAS exome

AF:

0.515

Gnomad4 SAS exome

AF:

0.663

Gnomad4 FIN exome

AF:

0.756

Gnomad4 NFE exome

AF:

0.666

Gnomad4 OTH exome

AF:

0.658

GnomAD4 genome

AF:

0.699

AC:

106361

AN:

152116

Hom.:

37672

Cov.:

AF XY:

0.699

AC XY:

51993

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.809

Gnomad4 AMR

AF:

0.608

Gnomad4 ASJ

AF:

0.644

Gnomad4 EAS

AF:

0.557

Gnomad4 SAS

AF:

0.669

Gnomad4 FIN

AF:

0.749

Gnomad4 NFE

AF:

0.663

Gnomad4 OTH

AF:

0.648

Alfa

AF:

0.662

Hom.:

67493

Bravo

AF:

0.691

TwinsUK

AF:

0.664

AC:

2462

ALSPAC

AF:

0.664

AC:

2559

ESP6500AA

AF:

0.810

AC:

3570

ESP6500EA

AF:

0.665

AC:

5722

ExAC

AF:

0.661

AC:

80304

Asia WGS

AF:

0.628

AC:

2186

AN:

3478

EpiCase

AF:

0.649

EpiControl

AF:

0.643

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Weill-Marchesani 4 syndrome, recessive

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, Amsterdam University Medical Center

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.53

DEOGEN2

Benign

0.012

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.35

MetaRNN

Benign

8.2e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

0.13

REVEL

Benign

0.089

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.089

MPC

0.074

ClinPred

0.0021

GERP RS

4.1

Varity_R

0.030

gMVP

0.31

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