chr16-77291428-G-T

Variant names:

Variant summary

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

The NM_199355.4(ADAMTS18):c.3240C>A(p.Ser1080Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,613,778 control chromosomes in the GnomAD database, including 172,834 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 0.35 ( 11676 hom., cov: 32)

Exomes 𝑓: 0.46 ( 161158 hom. )

Consequence

ADAMTS18
NM_199355.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.508

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 links:

ENSG00000260922 (HGNC:):

ENSG00000260922 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=1.0391632E-4).

BP6

Variant 16-77291428-G-T is Benign according to our data. Variant chr16-77291428-G-T is described in ClinVar as [Benign]. Clinvar id is 1166169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-77291428-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS18	NM_199355.4 link	c.3240C>A	p.Ser1080Arg	missense_variant	Exon 21 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.3240C>A	p.Ser1080Arg	missense_variant	Exon 21 of 23	1	NM_199355.4	ENSP00000282849.5		Q8TE60-1
ENSG00000260922	ENST00000648730.1 link	n.117+1973G>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53352

AN:

151904

Hom.:

11682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.580

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.501

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.493

Gnomad OTH

AF:

0.377

GnomAD3 exomes

AF:

0.378

AC:

94942

AN:

251316

Hom.:

20988

AF XY:

0.387

AC XY:

52633

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.0982

Gnomad AMR exome

AF:

0.214

Gnomad ASJ exome

AF:

0.499

Gnomad EAS exome

AF:

0.119

Gnomad SAS exome

AF:

0.309

Gnomad FIN exome

AF:

0.498

Gnomad NFE exome

AF:

0.492

Gnomad OTH exome

AF:

0.425

GnomAD4 exome

AF:

0.457

AC:

668527

AN:

1461756

Hom.:

161158

Cov.:

AF XY:

0.455

AC XY:

330570

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0980

Gnomad4 AMR exome

AF:

0.226

Gnomad4 ASJ exome

AF:

0.496

Gnomad4 EAS exome

AF:

0.129

Gnomad4 SAS exome

AF:

0.312

Gnomad4 FIN exome

AF:

0.503

Gnomad4 NFE exome

AF:

0.499

Gnomad4 OTH exome

AF:

0.429

GnomAD4 genome

AF:

0.351

AC:

53337

AN:

152022

Hom.:

11676

Cov.:

AF XY:

0.346

AC XY:

25700

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.301

Gnomad4 ASJ

AF:

0.493

Gnomad4 EAS

AF:

0.129

Gnomad4 SAS

AF:

0.320

Gnomad4 FIN

AF:

0.501

Gnomad4 NFE

AF:

0.493

Gnomad4 OTH

AF:

0.372

Alfa

AF:

0.452

Hom.:

14064

Bravo

AF:

0.327

TwinsUK

AF:

0.497

AC:

1843

ALSPAC

AF:

0.507

AC:

1955

ESP6500AA

AF:

0.119

AC:

525

ESP6500EA

AF:

0.495

AC:

4260

ExAC

AF:

0.377

AC:

45719

Asia WGS

AF:

0.180

AC:

629

AN:

3478

EpiCase

AF:

0.497

EpiControl

AF:

0.491

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.66

MetaRNN

Benign

0.00010

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.39

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.5

REVEL

Benign

0.036

Sift

Uncertain

0.012

Sift4G

Uncertain

0.013

Polyphen

0.19

Vest4

0.18

MutPred

0.29

Gain of MoRF binding (P = 0.0271);

ClinPred

0.042

GERP RS

-4.8

Varity_R

0.13

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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