Genetic Variant NM_139056.4:c.587A>G (chr5-5182129-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_139056.4(ADAMTS16):c.587A>G(p.Gln196Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000431 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00043 ( 0 hom. )

Consequence

ADAMTS16
NM_139056.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.606

Publications

5 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040360093).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS16	NM_139056.4	MANE Select	c.587A>G	p.Gln196Arg	missense	Exon 4 of 23	NP_620687.2	Q8TE57-1
	ADAMTS16	NR_136935.2		n.725A>G		non_coding_transcript_exon	Exon 4 of 22

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAMTS16	ENST00000274181.7	TSL:2 MANE Select	c.587A>G	p.Gln196Arg	missense	Exon 4 of 23	ENSP00000274181.7	Q8TE57-1
ADAMTS16	ENST00000511368.5	TSL:1	c.587A>G	p.Gln196Arg	missense	Exon 4 of 11	ENSP00000421631.1	Q2XQZ0
ADAMTS16	ENST00000433402.2	TSL:1	n.587A>G		non_coding_transcript_exon	Exon 4 of 20

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000747

AC:

186

AN:

248980

AF XY:

0.000747

show subpopulations

Gnomad AFR exome

AF:

0.0000649

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.00677

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000337

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.000426

AC:

622

AN:

1461702

Hom.:

Cov.:

AF XY:

0.000428

AC XY:

311

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33478

American (AMR)

AF:

0.00186

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00746

AC:

195

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53302

Middle Eastern (MID)

AF:

0.00850

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000191

AC:

212

AN:

1111950

Other (OTH)

AF:

0.00113

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

111

148

185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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

AF:

0.000486

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41580

American (AMR)

AF:

0.000915

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000730

Hom.:

Bravo

AF:

0.000608

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000729

AC:

ExAC

AF:

0.000422

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000652

ClinVar

ClinVar submissions

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

0.058

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.10

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.0080

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.30

M_CAP

Benign

0.0038

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.61

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.98

REVEL

Benign

0.045

Sift

Benign

0.33

Sift4G

Benign

0.10

Polyphen

0.0

Vest4

0.060

MVP

0.20

MPC

0.18

ClinPred

0.0088

GERP RS

-9.8

Varity_R

0.032

gMVP

0.30

Mutation Taster

=93/7

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over