chr16-77320076-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.2305C>A(p.Leu769Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,613,458 control chromosomes in the GnomAD database, including 166,153 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 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 0.52 ( 22941 hom., cov: 32)

Exomes 𝑓: 0.43 ( 143212 hom. )

Consequence

ADAMTS18
NM_199355.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.53

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:

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=2.776122E-6).

BP6

Variant 16-77320076-G-T is Benign according to our data. Variant chr16-77320076-G-T is described in ClinVar as [Benign]. Clinvar id is 1168652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-77320076-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS18	NM_199355.4 link	c.2305C>A	p.Leu769Ile	missense_variant	Exon 16 of 23	ENST00000282849.10	NP_955387.1	Q8TE60-1Q2VYF7Q6ZN25
ADAMTS18	NM_001326358.2 link	c.1789C>A	p.Leu597Ile	missense_variant	Exon 16 of 23		NP_001313287.1
ADAMTS18	XM_047433672.1 link	c.1789C>A	p.Leu597Ile	missense_variant	Exon 13 of 19		XP_047289628.1
ADAMTS18	XM_047433673.1 link	c.1069C>A	p.Leu357Ile	missense_variant	Exon 10 of 17		XP_047289629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS18	ENST00000282849.10 link	c.2305C>A	p.Leu769Ile	missense_variant	Exon 16 of 23	1	NM_199355.4	ENSP00000282849.5		Q8TE60-1
ADAMTS18	ENST00000568393.1 link	n.76C>A		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.523

AC:

79325

AN:

151788

Hom.:

22906

Cov.:

show subpopulations

Gnomad AFR

AF:

0.741

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.560

Gnomad ASJ

AF:

0.388

Gnomad EAS

AF:

0.878

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.501

GnomAD3 exomes

AF:

0.497

AC:

123742

AN:

249074

Hom.:

34267

AF XY:

0.483

AC XY:

65172

AN XY:

134856

show subpopulations

Gnomad AFR exome

AF:

0.753

Gnomad AMR exome

AF:

0.641

Gnomad ASJ exome

AF:

0.388

Gnomad EAS exome

AF:

0.884

Gnomad SAS exome

AF:

0.491

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.393

Gnomad OTH exome

AF:

0.458

GnomAD4 exome

AF:

0.428

AC:

626210

AN:

1461550

Hom.:

143212

Cov.:

AF XY:

0.428

AC XY:

311165

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.755

Gnomad4 AMR exome

AF:

0.631

Gnomad4 ASJ exome

AF:

0.388

Gnomad4 EAS exome

AF:

0.890

Gnomad4 SAS exome

AF:

0.494

Gnomad4 FIN exome

AF:

0.347

Gnomad4 NFE exome

AF:

0.392

Gnomad4 OTH exome

AF:

0.454

GnomAD4 genome

AF:

0.523

AC:

79408

AN:

151908

Hom.:

22941

Cov.:

AF XY:

0.523

AC XY:

38838

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.741

Gnomad4 AMR

AF:

0.560

Gnomad4 ASJ

AF:

0.388

Gnomad4 EAS

AF:

0.878

Gnomad4 SAS

AF:

0.485

Gnomad4 FIN

AF:

0.341

Gnomad4 NFE

AF:

0.396

Gnomad4 OTH

AF:

0.507

Alfa

AF:

0.431

Hom.:

36846

Bravo

AF:

0.551

TwinsUK

AF:

0.401

AC:

1488

ALSPAC

AF:

0.390

AC:

1504

ESP6500AA

AF:

0.748

AC:

3290

ESP6500EA

AF:

0.395

AC:

3395

ExAC

AF:

0.496

AC:

60203

Asia WGS

AF:

0.690

AC:

2395

AN:

3478

EpiCase

AF:

0.388

EpiControl

AF:

0.393

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

0.055

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.9

DANN

Benign

0.47

DEOGEN2

Benign

0.014

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0000028

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.045

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.040

REVEL

Benign

0.11

Sift

Benign

0.48

Sift4G

Benign

0.47

Polyphen

0.0

Vest4

0.042

ClinPred

0.0051

GERP RS

2.1

Varity_R

0.075

gMVP

0.33

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

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