rs4747096

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_080722.4(ADAMTS14):c.3146A>G(p.Glu1049Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,613,734 control chromosomes in the GnomAD database, including 27,609 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.19 ( 2801 hom., cov: 33)

Exomes 𝑓: 0.18 ( 24808 hom. )

Consequence

ADAMTS14
NM_080722.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.26

Variant links:

Genes affected

ADAMTS14 (HGNC:14899): (ADAM metallopeptidase with thrombospondin type 1 motif 14) 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 encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme cleaves amino-terminal propeptides from type I procollagen, a necessary step in the formation of collagen fibers. Mutations in this gene may be associated with osteoarthritis in human patients. [provided by RefSeq, May 2016]

ADAMTS14 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=0.004669875).

BP6

Variant 10-70758253-A-G is Benign according to our data. Variant chr10-70758253-A-G is described in ClinVar as [Benign]. Clinvar id is 1287457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS14	NM_080722.4 link	c.3146A>G	p.Glu1049Gly	missense_variant	Exon 21 of 22	ENST00000373207.2	NP_542453.2	Q8WXS8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS14	ENST00000373207.2 link	c.3146A>G	p.Glu1049Gly	missense_variant	Exon 21 of 22	1	NM_080722.4	ENSP00000362303.1		Q8WXS8-1
ADAMTS14	ENST00000373208.5 link	c.3155A>G	p.Glu1052Gly	missense_variant	Exon 21 of 22	2		ENSP00000362304.1		Q8WXS8-4

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28622

AN:

152084

Hom.:

2803

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.369

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.192

AC:

48305

AN:

251106

Hom.:

5095

AF XY:

0.188

AC XY:

25532

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.186

Gnomad AMR exome

AF:

0.228

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.352

Gnomad SAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.234

Gnomad NFE exome

AF:

0.168

Gnomad OTH exome

AF:

0.201

GnomAD4 exome

AF:

0.179

AC:

262019

AN:

1461532

Hom.:

24808

Cov.:

AF XY:

0.178

AC XY:

129417

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.185

Gnomad4 AMR exome

AF:

0.228

Gnomad4 ASJ exome

AF:

0.108

Gnomad4 EAS exome

AF:

0.380

Gnomad4 SAS exome

AF:

0.146

Gnomad4 FIN exome

AF:

0.234

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.179

GnomAD4 genome

AF:

0.188

AC:

28622

AN:

152202

Hom.:

2801

Cov.:

AF XY:

0.191

AC XY:

14213

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.186

Gnomad4 AMR

AF:

0.210

Gnomad4 ASJ

AF:

0.106

Gnomad4 EAS

AF:

0.369

Gnomad4 SAS

AF:

0.148

Gnomad4 FIN

AF:

0.238

Gnomad4 NFE

AF:

0.170

Gnomad4 OTH

AF:

0.180

Alfa

AF:

0.170

Hom.:

5193

Bravo

AF:

0.187

TwinsUK

AF:

0.166

AC:

617

ALSPAC

AF:

0.173

AC:

665

ESP6500AA

AF:

0.188

AC:

830

ESP6500EA

AF:

0.161

AC:

1387

ExAC

AF:

0.189

AC:

22882

Asia WGS

AF:

0.268

AC:

934

AN:

3478

EpiCase

AF:

0.162

EpiControl

AF:

0.164

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 23491141) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.8

DANN

Benign

0.32

DEOGEN2

Benign

0.0085

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.059

T;T

MetaRNN

Benign

0.0047

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.7

.;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.49

N;N

REVEL

Benign

0.059

Sift

Benign

0.67

T;T

Sift4G

Benign

0.43

T;T

Polyphen

0.0

.;B

Vest4

0.028

MPC

0.20

ClinPred

0.0012

GERP RS

3.0

Varity_R

0.029

gMVP

0.38

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