rs12935394

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_199355.4(ADAMTS18):c.2836G>T(p.Ala946Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,614,064 control chromosomes in the GnomAD database, including 14,034 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1012 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13022 hom. )

Consequence

ADAMTS18
NM_199355.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.15

Publications

22 publications found

Variant links:

Genes affected

ADAMTS18 (HGNC:17110): (ADAM metallopeptidase with thrombospondin type 1 motif 18) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS family members 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 protein, which may regulate hemostatic balance and function as a tumor suppressor. Mutations in this gene may be associated with microcornea, myopic chorioretinal atrophy, and telecanthus (MMCAT) and cone-rod dystrophy in human patients. [provided by RefSeq, May 2016]

ADAMTS18 Gene-Disease associations (from GenCC):

microcornea-myopic chorioretinal atrophy
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P
inherited retinal dystrophy
Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ADAMTS18 links:

ENSG00000260922 (HGNC:):

ENSG00000260922 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026280582).

BP6

Variant 16-77295093-C-A is Benign according to our data. Variant chr16-77295093-C-A is described in ClinVar as [Benign]. Clinvar id is 1166617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS18	NM_199355.4 link	c.2836G>T	p.Ala946Ser	missense_variant	Exon 19 of 23	ENST00000282849.10	NP_955387.1	Q8TE60-1Q2VYF7Q6ZN25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS18	ENST00000282849.10 link	c.2836G>T	p.Ala946Ser	missense_variant	Exon 19 of 23	1	NM_199355.4	ENSP00000282849.5		Q8TE60-1
ENSG00000260922	ENST00000648730.1 link	n.118-3797C>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15480

AN:

152102

Hom.:

1012

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0228

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.0782

Gnomad MID

AF:

0.0669

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.120

GnomAD2 exomes

AF:

0.135

AC:

33918

AN:

250998

AF XY:

0.134

show subpopulations

Gnomad AFR exome

AF:

0.0215

Gnomad AMR exome

AF:

0.210

Gnomad ASJ exome

AF:

0.191

Gnomad EAS exome

AF:

0.183

Gnomad FIN exome

AF:

0.0772

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.130

AC:

190155

AN:

1461844

Hom.:

13022

Cov.:

AF XY:

0.130

AC XY:

94657

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.0191

AC:

639

AN:

33480

American (AMR)

AF:

0.209

AC:

9366

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

5079

AN:

26136

East Asian (EAS)

AF:

0.191

AC:

7589

AN:

39698

South Asian (SAS)

AF:

0.133

AC:

11488

AN:

86254

European-Finnish (FIN)

AF:

0.0819

AC:

4372

AN:

53406

Middle Eastern (MID)

AF:

0.108

AC:

623

AN:

5768

European-Non Finnish (NFE)

AF:

0.129

AC:

143022

AN:

1111988

Other (OTH)

AF:

0.132

AC:

7977

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

10184

20368

30552

40736

50920

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.102

AC:

15476

AN:

152220

Hom.:

1012

Cov.:

AF XY:

0.102

AC XY:

7615

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0227

AC:

944

AN:

41554

American (AMR)

AF:

0.171

AC:

2610

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

644

AN:

3470

East Asian (EAS)

AF:

0.188

AC:

967

AN:

5148

South Asian (SAS)

AF:

0.117

AC:

565

AN:

4826

European-Finnish (FIN)

AF:

0.0782

AC:

830

AN:

10612

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.125

AC:

8517

AN:

68008

Other (OTH)

AF:

0.119

AC:

252

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

678

1357

2035

2714

3392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.121

Hom.:

4266

Bravo

AF:

0.108

TwinsUK

AF:

0.134

AC:

497

ALSPAC

AF:

0.123

AC:

474

ESP6500AA

AF:

0.0216

AC:

ESP6500EA

AF:

0.131

AC:

1125

ExAC

AF:

0.131

AC:

15912

Asia WGS

AF:

0.139

AC:

481

AN:

3478

EpiCase

AF:

0.127

EpiControl

AF:

0.133

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.95

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.0084

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.7

PhyloP100

1.1

PrimateAI

Benign

0.42

PROVEAN

Benign

1.5

REVEL

Benign

0.058

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.049

ClinPred

0.0051

GERP RS

3.3

Varity_R

0.032

gMVP

0.12

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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rs12935394

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over