16-77359310-G-C

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.1322+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,610,402 control chromosomes in the GnomAD database, including 263,511 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21928 hom., cov: 32)

Exomes 𝑓: 0.57 ( 241583 hom. )

Consequence

ADAMTS18
NM_199355.4 splice_region, intron

Scores

Splicing: ADA: 0.00003301

Clinical Significance

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

Conservation

PhyloP100: 0.229

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 (BayesDel_noAF=-0.82).

BP6

Variant 16-77359310-G-C is Benign according to our data. Variant chr16-77359310-G-C is described in ClinVar as [Benign]. Clinvar id is 1168654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-77359310-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS18	NM_199355.4 link	c.1322+8C>G	splice_region_variant, intron_variant	Intron 8 of 22	ENST00000282849.10	NP_955387.1	Q8TE60-1Q2VYF7Q6ZN25
ADAMTS18	NM_001326358.2 link	c.806+8C>G	splice_region_variant, intron_variant	Intron 8 of 22		NP_001313287.1
ADAMTS18	XM_047433672.1 link	c.806+8C>G	splice_region_variant, intron_variant	Intron 5 of 18		XP_047289628.1
ADAMTS18	XM_047433673.1 link	c.86+8C>G	splice_region_variant, intron_variant	Intron 2 of 16		XP_047289629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS18	ENST00000282849.10 link	c.1322+8C>G		splice_region_variant, intron_variant	Intron 8 of 22	1	NM_199355.4	ENSP00000282849.5		Q8TE60-1
ADAMTS18	ENST00000449265.2 link	n.*341+8C>G		splice_region_variant, intron_variant	Intron 7 of 7	2		ENSP00000392540.2		B4DEX3

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

80608

AN:

151936

Hom.:

21915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.500

Gnomad AMI

AF:

0.707

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.723

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.556

Gnomad FIN

AF:

0.489

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.586

Gnomad OTH

AF:

0.521

GnomAD3 exomes

AF:

0.514

AC:

127533

AN:

248346

Hom.:

34770

AF XY:

0.527

AC XY:

70611

AN XY:

134008

show subpopulations

Gnomad AFR exome

AF:

0.497

Gnomad AMR exome

AF:

0.266

Gnomad ASJ exome

AF:

0.729

Gnomad EAS exome

AF:

0.340

Gnomad SAS exome

AF:

0.560

Gnomad FIN exome

AF:

0.494

Gnomad NFE exome

AF:

0.591

Gnomad OTH exome

AF:

0.529

GnomAD4 exome

AF:

0.569

AC:

830346

AN:

1458348

Hom.:

241583

Cov.:

AF XY:

0.570

AC XY:

413409

AN XY:

725388

show subpopulations

Gnomad4 AFR exome

AF:

0.503

Gnomad4 AMR exome

AF:

0.282

Gnomad4 ASJ exome

AF:

0.730

Gnomad4 EAS exome

AF:

0.302

Gnomad4 SAS exome

AF:

0.562

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.593

Gnomad4 OTH exome

AF:

0.571

GnomAD4 genome

AF:

0.530

AC:

80635

AN:

152054

Hom.:

21928

Cov.:

AF XY:

0.522

AC XY:

38821

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.500

Gnomad4 AMR

AF:

0.401

Gnomad4 ASJ

AF:

0.723

Gnomad4 EAS

AF:

0.340

Gnomad4 SAS

AF:

0.556

Gnomad4 FIN

AF:

0.489

Gnomad4 NFE

AF:

0.586

Gnomad4 OTH

AF:

0.516

Alfa

AF:

0.584

Hom.:

8448

Bravo

AF:

0.522

Asia WGS

AF:

0.436

AC:

1522

AN:

3478

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

-0.82

CADD

Benign

6.3

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000033

dbscSNV1_RF

Benign

0.0

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