rs28567966

Positions:

chr15-100152640-A-G

Variant summary

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

The NM_139057.4(ADAMTS17):c.1445T>C(p.Met482Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,936 control chromosomes in the GnomAD database, including 18,976 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 (★★).

Frequency

Genomes: 𝑓 0.16 ( 2015 hom., cov: 32)

Exomes 𝑓: 0.15 ( 16961 hom. )

Consequence

ADAMTS17
NM_139057.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.60

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:

ADAMTS17 (HGNC:):

ADAMTS17 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036643445).

BP6

Variant 15-100152640-A-G is Benign according to our data. Variant chr15-100152640-A-G is described in ClinVar as [Benign]. Clinvar id is 315290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-100152640-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 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.1445T>C	p.Met482Thr	missense_variant	10/22	ENST00000268070.9	NP_620688.2	Q8TE56-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADAMTS17	ENST00000268070.9 linkuse as main transcript	c.1445T>C	p.Met482Thr	missense_variant	10/22	1	NM_139057.4	ENSP00000268070.4	Q8TE56-1
ADAMTS17	ENST00000568565.2 linkuse as main transcript	c.1445T>C	p.Met482Thr	missense_variant	10/23	5		ENSP00000456161.2	H3BRA9
ADAMTS17	ENST00000378898.8 linkuse as main transcript	n.1126T>C		non_coding_transcript_exon_variant	9/15	2

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23663

AN:

152016

Hom.:

2008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.206

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.0592

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.0862

Gnomad MID

AF:

0.172

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.164

GnomAD3 exomes

AF:

0.141

AC:

35439

AN:

251380

Hom.:

2855

AF XY:

0.145

AC XY:

19744

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.0848

Gnomad ASJ exome

AF:

0.220

Gnomad EAS exome

AF:

0.0558

Gnomad SAS exome

AF:

0.195

Gnomad FIN exome

AF:

0.0914

Gnomad NFE exome

AF:

0.149

Gnomad OTH exome

AF:

0.153

GnomAD4 exome

AF:

0.148

AC:

216343

AN:

1461802

Hom.:

16961

Cov.:

AF XY:

0.150

AC XY:

109272

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.0879

Gnomad4 ASJ exome

AF:

0.219

Gnomad4 EAS exome

AF:

0.0606

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.0960

Gnomad4 NFE exome

AF:

0.148

Gnomad4 OTH exome

AF:

0.156

GnomAD4 genome

AF:

0.156

AC:

23694

AN:

152134

Hom.:

2015

Cov.:

AF XY:

0.152

AC XY:

11322

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.201

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.222

Gnomad4 EAS

AF:

0.0594

Gnomad4 SAS

AF:

0.185

Gnomad4 FIN

AF:

0.0862

Gnomad4 NFE

AF:

0.149

Gnomad4 OTH

AF:

0.162

Alfa

AF:

0.151

Hom.:

2876

Bravo

AF:

0.159

TwinsUK

AF:

0.156

AC:

579

ALSPAC

AF:

0.153

AC:

590

ESP6500AA

AF:

0.200

AC:

881

ESP6500EA

AF:

0.149

AC:

1279

ExAC

AF:

0.146

AC:

17675

Asia WGS

AF:

0.111

AC:

389

AN:

3478

EpiCase

AF:

0.151

EpiControl

AF:

0.151

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	GeneDx	Sep 04, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Weill-Marchesani 4 syndrome, recessive

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.041

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.9

DANN

Benign

0.29

DEOGEN2

Benign

0.016

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.057

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.7

PrimateAI

Uncertain

0.66

PROVEAN

Benign

2.1

REVEL

Benign

0.029

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.10

MPC

0.11

ClinPred

0.0012

GERP RS

2.6

Varity_R

0.036

gMVP

0.36

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