dbSNP rs781606784: ADAMTS16:p.Ser153Thr (chr5-5146411-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_139056.4(ADAMTS16):c.457T>A(p.Ser153Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,460,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ADAMTS16
NM_139056.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

Publications

0 publications found

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:

ADAMTS16-AS1 (HGNC:58093):

ADAMTS16-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20756057).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139056.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAMTS16	NM_139056.4	MANE Select	c.457T>A	p.Ser153Thr	missense	Exon 3 of 23	NP_620687.2	Q8TE57-1
ADAMTS16	NR_136935.2		n.595T>A		non_coding_transcript_exon	Exon 3 of 22
ADAMTS16-AS1	NR_198969.1		n.221-4040A>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAMTS16	ENST00000274181.7	TSL:2 MANE Select	c.457T>A	p.Ser153Thr	missense	Exon 3 of 23	ENSP00000274181.7	Q8TE57-1
ADAMTS16	ENST00000511368.5	TSL:1	c.457T>A	p.Ser153Thr	missense	Exon 3 of 11	ENSP00000421631.1	Q2XQZ0
ADAMTS16	ENST00000433402.2	TSL:1	n.457T>A		non_coding_transcript_exon	Exon 3 of 20

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000362

AC:

AN:

248290

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000501

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1460960

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726828

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000579

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111992

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000414

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.017

Eigen

Benign

-0.073

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.56

M_CAP

Benign

0.0056

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

PhyloP100

1.8

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.5

REVEL

Benign

0.14

Sift

Benign

0.27

Sift4G

Benign

0.10

Polyphen

0.78

Vest4

0.30

MutPred

0.68

Loss of disorder (P = 0.0583)

MVP

0.60

MPC

0.26

ClinPred

0.17

GERP RS

1.9

Varity_R

0.24

gMVP

0.43

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over