rs12935229

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_199355.4(ADAMTS18):c.2931G>A(p.Val977Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,614,014 control chromosomes in the GnomAD database, including 14,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1019 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13005 hom. )

Consequence

ADAMTS18
NM_199355.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.960

Publications

15 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 16-77294998-C-T is Benign according to our data. Variant chr16-77294998-C-T is described in ClinVar as [Benign]. Clinvar id is 1166616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.96 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS18	NM_199355.4 link	c.2931G>A	p.Val977Val	synonymous_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.2931G>A	p.Val977Val	synonymous_variant	Exon 19 of 23	1	NM_199355.4	ENSP00000282849.5		Q8TE60-1
ENSG00000260922	ENST00000648730.1 link	n.118-3892C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15490

AN:

152088

Hom.:

1018

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:

0.188

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.0783

Gnomad MID

AF:

0.0673

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.121

GnomAD2 exomes

AF:

0.135

AC:

33896

AN:

251280

AF XY:

0.134

show subpopulations

Gnomad AFR exome

AF:

0.0215

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.191

Gnomad EAS exome

AF:

0.184

Gnomad FIN exome

AF:

0.0770

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.130

AC:

190097

AN:

1461806

Hom.:

13005

Cov.:

AF XY:

0.130

AC XY:

94645

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.0191

AC:

639

AN:

33480

American (AMR)

AF:

0.208

AC:

9305

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

5079

AN:

26136

East Asian (EAS)

AF:

0.191

AC:

7580

AN:

39694

South Asian (SAS)

AF:

0.133

AC:

11489

AN:

86256

European-Finnish (FIN)

AF:

0.0819

AC:

4373

AN:

53406

Middle Eastern (MID)

AF:

0.108

AC:

623

AN:

5768

European-Non Finnish (NFE)

AF:

0.129

AC:

143028

AN:

1111958

Other (OTH)

AF:

0.132

AC:

7981

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

10146

20292

30438

40584

50730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5286

10572

15858

21144

26430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.102

AC:

15488

AN:

152208

Hom.:

1019

Cov.:

AF XY:

0.102

AC XY:

7628

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0227

AC:

944

AN:

41548

American (AMR)

AF:

0.171

AC:

2610

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

646

AN:

3470

East Asian (EAS)

AF:

0.189

AC:

976

AN:

5164

South Asian (SAS)

AF:

0.117

AC:

563

AN:

4818

European-Finnish (FIN)

AF:

0.0783

AC:

830

AN:

10600

Middle Eastern (MID)

AF:

0.0651

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.125

AC:

8520

AN:

68018

Other (OTH)

AF:

0.119

AC:

252

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

705

1410

2116

2821

3526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.121

Hom.:

3973

Bravo

AF:

0.108

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

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.96

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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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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