Variant chr5-5187717-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_139056.4(ADAMTS16):c.964-8T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,603,808 control chromosomes in the GnomAD database, including 4 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 3 hom. )

Consequence

ADAMTS16
NM_139056.4 splice_region, intron

Scores

Splicing: ADA: 0.0003395

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0910

Variant links:

Genes affected

ADAMTS16 (HGNC:17108): (ADAM metallopeptidase with thrombospondin type 1 motif 16) 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 inhibit chondrosarcoma cell proliferation and migration. This gene may regulate blood pressure. [provided by RefSeq, May 2016]

ADAMTS16 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-5187717-T-A is Benign according to our data. Variant chr5-5187717-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2655282.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS16	NM_139056.4 link	c.964-8T>A	splice_region_variant, intron_variant	Intron 5 of 22	ENST00000274181.7	NP_620687.2	Q8TE57-1Q2XQZ0
ADAMTS16	XM_047416874.1 link	c.964-8T>A	splice_region_variant, intron_variant	Intron 5 of 21		XP_047272830.1
ADAMTS16	XM_047416875.1 link	c.964-8T>A	splice_region_variant, intron_variant	Intron 5 of 19		XP_047272831.1
ADAMTS16	NR_136935.2 link	n.1102-8T>A	splice_region_variant, intron_variant	Intron 5 of 21

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADAMTS16	ENST00000274181.7 link	c.964-8T>A	splice_region_variant, intron_variant	Intron 5 of 22	2	NM_139056.4	ENSP00000274181.7	Q8TE57-1
ADAMTS16	ENST00000511368.5 link	c.964-8T>A	splice_region_variant, intron_variant	Intron 5 of 10	1		ENSP00000421631.1	Q2XQZ0
ADAMTS16	ENST00000433402.2 link	n.964-8T>A	splice_region_variant, intron_variant	Intron 5 of 19	1

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

182

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00429

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000270

AC:

AN:

248422

Hom.:

AF XY:

0.000148

AC XY:

AN XY:

134754

show subpopulations

Gnomad AFR exome

AF:

0.00401

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000121

AC:

175

AN:

1451478

Hom.:

Cov.:

AF XY:

0.0000899

AC XY:

AN XY:

722734

show subpopulations

Gnomad4 AFR exome

AF:

0.00454

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000363

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.00119

AC:

182

AN:

152330

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00428

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000313

Hom.:

Bravo

AF:

0.00119

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ADAMTS16: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.5

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00034

dbscSNV1_RF

Benign

0.076

SpliceAI score (max)

0.010

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