5-5182129-A-G

Position:

chr5-5182129-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 15/21 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

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADAMTS16	NM_139056.4 linkuse as main transcript	c.587A>G	p.Gln196Arg	missense_variant	4/23	ENST00000274181.7	NP_620687.2
ADAMTS16	XM_047416874.1 linkuse as main transcript	c.587A>G	p.Gln196Arg	missense_variant	4/22		XP_047272830.1
ADAMTS16	XM_047416875.1 linkuse as main transcript	c.587A>G	p.Gln196Arg	missense_variant	4/20		XP_047272831.1
ADAMTS16	NR_136935.2 linkuse as main transcript	n.725A>G		non_coding_transcript_exon_variant	4/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS16	ENST00000274181.7 linkuse as main transcript	c.587A>G	p.Gln196Arg	missense_variant	4/23	2	NM_139056.4	ENSP00000274181	P1	Q8TE57-1
ADAMTS16	ENST00000511368.5 linkuse as main transcript	c.587A>G	p.Gln196Arg	missense_variant	4/11	1		ENSP00000421631
ADAMTS16	ENST00000433402.2 linkuse as main transcript	n.587A>G		non_coding_transcript_exon_variant	4/20	1

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

GnomAD3 exomes

AF:

0.000747

AC:

186

AN:

248980

Hom.:

AF XY:

0.000747

AC XY:

101

AN XY:

135232

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 SAS exome

AF:

0.0000980

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

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00186

Gnomad4 ASJ exome

AF:

0.00746

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000191

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.000486

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000777

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.587A>G (p.Q196R) alteration is located in exon 4 (coding exon 4) of the ADAMTS16 gene. This alteration results from a A to G substitution at nucleotide position 587, causing the glutamine (Q) at amino acid position 196 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.10

DANN

Benign

0.57

DEOGEN2

Benign

0.0080

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.30

T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.0040

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.98

N;N

REVEL

Benign

0.045

Sift

Benign

0.33

T;T

Sift4G

Benign

0.10

T;D

Polyphen

0.0

B;B

Vest4

0.060

MVP

0.20

MPC

0.18

ClinPred

0.0088

GERP RS

-9.8

Varity_R

0.032

gMVP

0.30

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

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