Variant chr10-70760503-C-T 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.3322C>T(p.Pro1108Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0932 in 1,613,844 control chromosomes in the GnomAD database, including 7,622 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.076 ( 572 hom., cov: 33)

Exomes 𝑓: 0.095 ( 7050 hom. )

Consequence

ADAMTS14
NM_080722.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0920

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017440319).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 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.3322C>T	p.Pro1108Ser	missense_variant	22/22	ENST00000373207.2	NP_542453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS14	ENST00000373207.2 linkuse as main transcript	c.3322C>T	p.Pro1108Ser	missense_variant	22/22	1	NM_080722.4	ENSP00000362303	P4	Q8WXS8-1
ADAMTS14	ENST00000373208.5 linkuse as main transcript	c.3331C>T	p.Pro1111Ser	missense_variant	22/22	2		ENSP00000362304	A2	Q8WXS8-4

Frequencies

GnomAD3 genomes

AF:

0.0758

AC:

11539

AN:

152130

Hom.:

571

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0187

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.0543

Gnomad ASJ

AF:

0.0862

Gnomad EAS

AF:

0.0980

Gnomad SAS

AF:

0.0739

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.0801

GnomAD3 exomes

AF:

0.0857

AC:

21298

AN:

248402

Hom.:

1070

AF XY:

0.0883

AC XY:

11869

AN XY:

134484

show subpopulations

Gnomad AFR exome

AF:

0.0164

Gnomad AMR exome

AF:

0.0412

Gnomad ASJ exome

AF:

0.0825

Gnomad EAS exome

AF:

0.0941

Gnomad SAS exome

AF:

0.0764

Gnomad FIN exome

AF:

0.134

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.0931

GnomAD4 exome

AF:

0.0951

AC:

138940

AN:

1461596

Hom.:

7050

Cov.:

AF XY:

0.0949

AC XY:

69015

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.0150

Gnomad4 AMR exome

AF:

0.0436

Gnomad4 ASJ exome

AF:

0.0806

Gnomad4 EAS exome

AF:

0.0798

Gnomad4 SAS exome

AF:

0.0776

Gnomad4 FIN exome

AF:

0.132

Gnomad4 NFE exome

AF:

0.100

Gnomad4 OTH exome

AF:

0.0890

GnomAD4 genome

AF:

0.0757

AC:

11523

AN:

152248

Hom.:

572

Cov.:

AF XY:

0.0761

AC XY:

5663

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0187

Gnomad4 AMR

AF:

0.0542

Gnomad4 ASJ

AF:

0.0862

Gnomad4 EAS

AF:

0.0974

Gnomad4 SAS

AF:

0.0731

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.103

Gnomad4 OTH

AF:

0.0792

Alfa

AF:

0.0884

Hom.:

279

Bravo

AF:

0.0694

TwinsUK

AF:

0.0998

AC:

370

ALSPAC

AF:

0.104

AC:

399

ESP6500AA

AF:

0.0245

AC:

108

ESP6500EA

AF:

0.105

AC:

906

ExAC

AF:

0.0871

AC:

10577

Asia WGS

AF:

0.0720

AC:

251

AN:

3478

EpiCase

AF:

0.0990

EpiControl

AF:

0.0982

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.36

DANN

Benign

0.24

DEOGEN2

Benign

0.011

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.39

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.94

.;L

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.24

N;N

REVEL

Benign

0.013

Sift

Benign

0.87

T;T

Sift4G

Benign

0.87

T;T

Polyphen

0.0020

.;B

Vest4

0.022

MPC

0.17

ClinPred

0.00042

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.017

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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