5-5146238-A-G

Position:

chr5-5146238-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.284A>G(p.Glu95Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 1,614,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

ADAMTS16
NM_139056.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.03

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:

ENSG00000250866 (HGNC:58093):

ENSG00000250866 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=0.01900199).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS16	NM_139056.4 link	c.284A>G	p.Glu95Gly	missense_variant	3/23	ENST00000274181.7	NP_620687.2	Q8TE57-1Q2XQZ0
ADAMTS16	XM_047416874.1 link	c.284A>G	p.Glu95Gly	missense_variant	3/22		XP_047272830.1
ADAMTS16	XM_047416875.1 link	c.284A>G	p.Glu95Gly	missense_variant	3/20		XP_047272831.1
ADAMTS16	NR_136935.2 link	n.422A>G		non_coding_transcript_exon_variant	3/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADAMTS16	ENST00000274181.7 link	c.284A>G	p.Glu95Gly	missense_variant	3/23	2	NM_139056.4	ENSP00000274181.7	Q8TE57-1
ADAMTS16	ENST00000511368.5 link	c.284A>G	p.Glu95Gly	missense_variant	3/11	1		ENSP00000421631.1	Q2XQZ0
ADAMTS16	ENST00000433402.2 link	n.284A>G		non_coding_transcript_exon_variant	3/20	1
ENSG00000250866	ENST00000514848.1 link	n.221-3867T>C		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000144

AC:

AN:

249556

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000230

AC:

336

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

172

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000777

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000230

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000947

Hom.:

Bravo

AF:

0.0000491

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Oct 26, 2021

The c.284A>G (p.E95G) alteration is located in exon 3 (coding exon 3) of the ADAMTS16 gene. This alteration results from a A to G substitution at nucleotide position 284, causing the glutamic acid (E) at amino acid position 95 to be replaced by a glycine (G). 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

0.068

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.012

.;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.29

T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.52

.;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.077

Sift

Benign

0.22

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.0

B;B

Vest4

0.044

MVP

0.39

MPC

0.19

ClinPred

0.043

GERP RS

1.3

Varity_R

0.052

gMVP

0.38

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