Variant rs12774070 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080722.4(ADAMTS14):c.2809C>A(p.Leu937Met) variant causes a missense change. The variant allele was found at a frequency of 0.252 in 1,591,176 control chromosomes in the GnomAD database, including 52,905 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.20 ( 3602 hom., cov: 34)

Exomes 𝑓: 0.26 ( 49303 hom. )

Consequence

ADAMTS14
NM_080722.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.06

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016207993).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS14	NM_080722.4 linkuse as main transcript	c.2809C>A	p.Leu937Met	missense_variant	19/22	ENST00000373207.2	NP_542453.2	Q8WXS8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS14	ENST00000373207.2 linkuse as main transcript	c.2809C>A	p.Leu937Met	missense_variant	19/22	1	NM_080722.4	ENSP00000362303.1		Q8WXS8-1
ADAMTS14	ENST00000373208.5 linkuse as main transcript	c.2818C>A	p.Leu940Met	missense_variant	19/22	2		ENSP00000362304.1		Q8WXS8-4

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

29907

AN:

152112

Hom.:

3607

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0512

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.208

GnomAD3 exomes

AF:

0.228

AC:

47791

AN:

209372

Hom.:

5849

AF XY:

0.235

AC XY:

26413

AN XY:

112402

show subpopulations

Gnomad AFR exome

AF:

0.0486

Gnomad AMR exome

AF:

0.172

Gnomad ASJ exome

AF:

0.212

Gnomad EAS exome

AF:

0.159

Gnomad SAS exome

AF:

0.222

Gnomad FIN exome

AF:

0.264

Gnomad NFE exome

AF:

0.278

Gnomad OTH exome

AF:

0.239

GnomAD4 exome

AF:

0.258

AC:

370586

AN:

1438946

Hom.:

49303

Cov.:

AF XY:

0.257

AC XY:

183553

AN XY:

713096

show subpopulations

Gnomad4 AFR exome

AF:

0.0442

Gnomad4 AMR exome

AF:

0.176

Gnomad4 ASJ exome

AF:

0.205

Gnomad4 EAS exome

AF:

0.161

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.256

Gnomad4 NFE exome

AF:

0.275

Gnomad4 OTH exome

AF:

0.236

GnomAD4 genome

AF:

0.196

AC:

29887

AN:

152230

Hom.:

3602

Cov.:

AF XY:

0.196

AC XY:

14620

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0510

Gnomad4 AMR

AF:

0.205

Gnomad4 ASJ

AF:

0.209

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.216

Gnomad4 FIN

AF:

0.262

Gnomad4 NFE

AF:

0.272

Gnomad4 OTH

AF:

0.207

Alfa

AF:

0.236

Hom.:

2235

Bravo

AF:

0.186

TwinsUK

AF:

0.270

AC:

1003

ALSPAC

AF:

0.287

AC:

1105

ESP6500AA

AF:

0.0602

AC:

265

ESP6500EA

AF:

0.264

AC:

2270

ExAC

AF:

0.208

AC:

24994

Asia WGS

AF:

0.180

AC:

625

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

.;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.58

T;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;L

PrimateAI

Benign

0.41

PROVEAN

Benign

1.2

N;N

REVEL

Benign

0.15

Sift

Benign

0.17

T;T

Sift4G

Uncertain

0.010

D;D

Polyphen

0.99

.;D

Vest4

0.13

MPC

0.64

ClinPred

0.012

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over