NM_006988.5:c.2267G>A

Variant names:

Variant summary

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

The NM_006988.5(ADAMTS1):c.2267G>A(p.Arg756Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,613,836 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R756W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 22 hom. )

Consequence

ADAMTS1
NM_006988.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.57

Variant links:

Genes affected

ADAMTS1 (HGNC:217): (ADAM metallopeptidase with thrombospondin type 1 motif 1) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) 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. The protein encoded by this gene contains two disintegrin loops and three C-terminal TS motifs and has anti-angiogenic activity. The expression of this gene may be associated with various inflammatory processes as well as development of cancer cachexia. This gene is likely to be necessary for normal growth, fertility, and organ morphology and function. [provided by RefSeq, Jul 2008]

ADAMTS1 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=0.010748833).

BP6

Variant 21-26838216-C-T is Benign according to our data. Variant chr21-26838216-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 774534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 369 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS1	NM_006988.5 link	c.2267G>A	p.Arg756Gln	missense_variant	Exon 9 of 9	ENST00000284984.8	NP_008919.3	Q9UHI8B2RB33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS1	ENST00000284984.8 link	c.2267G>A	p.Arg756Gln	missense_variant	Exon 9 of 9	1	NM_006988.5	ENSP00000284984.2		Q9UHI8

Frequencies

GnomAD3 genomes

AF:

0.00243

AC:

369

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00560

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00398

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00276

AC:

693

AN:

250878

Hom.:

AF XY:

0.00322

AC XY:

437

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.000864

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00677

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00369

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00408

AC:

5966

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

3056

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00685

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.00451

Gnomad4 OTH exome

AF:

0.00394

GnomAD4 genome

AF:

0.00242

AC:

369

AN:

152176

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

168

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00104

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00561

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00398

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00350

Hom.:

Bravo

AF:

0.00244

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00306

AC:

372

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00344

EpiControl

AF:

0.00486

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.029

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.31

Sift

Benign

0.16

Sift4G

Benign

0.088

Polyphen

0.80

Vest4

0.65

MVP

0.93

MPC

0.97

ClinPred

0.051

GERP RS

5.7

Varity_R

0.13

gMVP

0.72

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