16-77367648-A-G

Position:

chr16-77367648-A-G

Variant summary

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

The ENST00000282849.10(ADAMTS18):c.571T>C(p.Tyr191His) variant causes a missense change. The variant allele was found at a frequency of 0.272 in 1,613,874 control chromosomes in the GnomAD database, including 66,120 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. Y191Y) has been classified as Benign.

Frequency

Genomes: 𝑓 0.28 ( 6697 hom., cov: 32)

Exomes 𝑓: 0.27 ( 59423 hom. )

Consequence

ADAMTS18
ENST00000282849.10 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 7.16

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=2.5203824E-4).

BP6

Variant 16-77367648-A-G is Benign according to our data. Variant chr16-77367648-A-G is described in ClinVar as [Benign]. Clinvar id is 803274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-77367648-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADAMTS18	NM_199355.4 linkuse as main transcript	c.571T>C	p.Tyr191His	missense_variant	4/23	ENST00000282849.10	NP_955387.1
ADAMTS18	NM_001326358.2 linkuse as main transcript	c.51T>C	p.Thr17=	synonymous_variant	4/23		NP_001313287.1
ADAMTS18	XM_047433672.1 linkuse as main transcript	c.51T>C	p.Thr17=	synonymous_variant	1/19		XP_047289628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS18	ENST00000282849.10 linkuse as main transcript	c.571T>C	p.Tyr191His	missense_variant	4/23	1	NM_199355.4	ENSP00000282849	P1	Q8TE60-1

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43142

AN:

151894

Hom.:

6679

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.437

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.577

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.318

GnomAD3 exomes

AF:

0.326

AC:

82059

AN:

251388

Hom.:

15870

AF XY:

0.315

AC XY:

42758

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.254

Gnomad AMR exome

AF:

0.582

Gnomad ASJ exome

AF:

0.191

Gnomad EAS exome

AF:

0.572

Gnomad SAS exome

AF:

0.297

Gnomad FIN exome

AF:

0.262

Gnomad NFE exome

AF:

0.252

Gnomad OTH exome

AF:

0.322

GnomAD4 exome

AF:

0.271

AC:

395856

AN:

1461862

Hom.:

59423

Cov.:

AF XY:

0.270

AC XY:

196678

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.253

Gnomad4 AMR exome

AF:

0.565

Gnomad4 ASJ exome

AF:

0.188

Gnomad4 EAS exome

AF:

0.624

Gnomad4 SAS exome

AF:

0.295

Gnomad4 FIN exome

AF:

0.262

Gnomad4 NFE exome

AF:

0.247

Gnomad4 OTH exome

AF:

0.277

GnomAD4 genome

AF:

0.284

AC:

43182

AN:

152012

Hom.:

6697

Cov.:

AF XY:

0.289

AC XY:

21445

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.252

Gnomad4 AMR

AF:

0.437

Gnomad4 ASJ

AF:

0.198

Gnomad4 EAS

AF:

0.578

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.257

Gnomad4 NFE

AF:

0.254

Gnomad4 OTH

AF:

0.325

Alfa

AF:

0.265

Hom.:

12912

Bravo

AF:

0.300

TwinsUK

AF:

0.221

AC:

819

ALSPAC

AF:

0.259

AC:

998

ESP6500AA

AF:

0.260

AC:

1145

ESP6500EA

AF:

0.249

AC:

2138

ExAC

AF:

0.316

AC:

38333

Asia WGS

AF:

0.445

AC:

1543

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Microcornea-myopic chorioretinal atrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.00025

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.000031

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.6

REVEL

Benign

0.24

Sift

Benign

0.43

Sift4G

Benign

0.27

Polyphen

0.60

Vest4

0.096

ClinPred

0.030

GERP RS

4.7

Varity_R

0.30

gMVP

0.53

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