Variant 4-72283534-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014243.3(ADAMTS3):c.3220T>C(p.Ser1074Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00412 in 1,614,070 control chromosomes in the GnomAD database, including 213 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.021 ( 112 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 101 hom. )

Consequence

ADAMTS3
NM_014243.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.67

Variant links:

Genes affected

ADAMTS3 (HGNC:219): (ADAM metallopeptidase with thrombospondin type 1 motif 3) 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. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease, a member of the procollagen aminopropeptidase subfamily of proteins, may play a role in the processing of type II fibrillar collagen in articular cartilage. [provided by RefSeq, Feb 2016]

ADAMTS3 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=0.0020766258).

BP6

Variant 4-72283534-A-G is Benign according to our data. Variant chr4-72283534-A-G is described in ClinVar as [Benign]. Clinvar id is 716108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-72283534-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADAMTS3	NM_014243.3 linkuse as main transcript	c.3220T>C	p.Ser1074Pro	missense_variant	22/22	ENST00000286657.10
ADAMTS3	XM_011532421.2 linkuse as main transcript	c.3163T>C	p.Ser1055Pro	missense_variant	22/22
ADAMTS3	XM_011532422.4 linkuse as main transcript	c.3136T>C	p.Ser1046Pro	missense_variant	22/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS3	ENST00000286657.10 linkuse as main transcript	c.3220T>C	p.Ser1074Pro	missense_variant	22/22	1	NM_014243.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0211

AC:

3208

AN:

152132

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0735

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00740

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00555

AC:

1393

AN:

251202

Hom.:

AF XY:

0.00403

AC XY:

547

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.0732

Gnomad AMR exome

AF:

0.00370

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00235

AC:

3433

AN:

1461820

Hom.:

101

Cov.:

AF XY:

0.00210

AC XY:

1527

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0773

Gnomad4 AMR exome

AF:

0.00411

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000638

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000239

Gnomad4 OTH exome

AF:

0.00500

GnomAD4 genome

AF:

0.0211

AC:

3220

AN:

152250

Hom.:

112

Cov.:

AF XY:

0.0201

AC XY:

1498

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0735

Gnomad4 AMR

AF:

0.00739

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00424

Hom.:

Bravo

AF:

0.0242

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0658

AC:

290

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00693

AC:

841

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0085

T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.58

.;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

1.1

N;.

REVEL

Benign

0.058

Sift

Benign

0.22

T;.

Sift4G

Benign

0.27

T;T

Polyphen

0.0

B;B

Vest4

0.081

MVP

0.60

MPC

0.15

ClinPred

0.012

GERP RS

4.3

Varity_R

0.10

gMVP

0.49

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