Variant rs12935229 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 -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. Variant chr16-77294998-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
ADAMTS18	NM_199355.4 linkuse as main transcript	c.2931G>A	p.Val977Val	synonymous_variant	19/23	ENST00000282849.10	NP_955387.1	Q8TE60-1Q2VYF7Q6ZN25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS18	ENST00000282849.10 linkuse as main transcript	c.2931G>A	p.Val977Val	synonymous_variant	19/23	1	NM_199355.4	ENSP00000282849.5		Q8TE60-1
ENSG00000260922	ENST00000648730.1 linkuse as main transcript	n.118-3892C>T		intron_variant

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

GnomAD3 exomes

AF:

0.135

AC:

33896

AN:

251280

Hom.:

2698

AF XY:

0.134

AC XY:

18194

AN XY:

135810

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 SAS exome

AF:

0.132

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

Gnomad4 AFR exome

AF:

0.0191

Gnomad4 AMR exome

AF:

0.208

Gnomad4 ASJ exome

AF:

0.194

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.0819

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.102

AC:

15488

AN:

152208

Hom.:

1019

Cov.:

AF XY:

0.102

AC XY:

7628

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0227

Gnomad4 AMR

AF:

0.171

Gnomad4 ASJ

AF:

0.186

Gnomad4 EAS

AF:

0.189

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.0783

Gnomad4 NFE

AF:

0.125

Gnomad4 OTH

AF:

0.119

Alfa

AF:

0.126

Hom.:

2567

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

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.80

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

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