5-5186054-A-G

Position:

chr5-5186054-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139056.4(ADAMTS16):c.766A>G(p.Met256Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,460,082 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.88

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13707206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS16	NM_139056.4 link	c.766A>G	p.Met256Val	missense_variant, splice_region_variant	5/23	ENST00000274181.7	NP_620687.2	Q8TE57-1Q2XQZ0
ADAMTS16	XM_047416874.1 link	c.766A>G	p.Met256Val	missense_variant, splice_region_variant	5/22		XP_047272830.1
ADAMTS16	XM_047416875.1 link	c.766A>G	p.Met256Val	missense_variant, splice_region_variant	5/20		XP_047272831.1
ADAMTS16	NR_136935.2 link	n.904A>G		splice_region_variant, non_coding_transcript_exon_variant	5/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADAMTS16	ENST00000274181.7 link	c.766A>G	p.Met256Val	missense_variant, splice_region_variant	5/23	2	NM_139056.4	ENSP00000274181.7	Q8TE57-1
ADAMTS16	ENST00000511368.5 link	c.766A>G	p.Met256Val	missense_variant, splice_region_variant	5/11	1		ENSP00000421631.1	Q2XQZ0
ADAMTS16	ENST00000433402.2 link	n.766A>G		splice_region_variant, non_coding_transcript_exon_variant	5/20	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

248274

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1460082

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726316

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000207

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.000109

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

Mar 19, 2024

The c.766A>G (p.M256V) alteration is located in exon 5 (coding exon 5) of the ADAMTS16 gene. This alteration results from a A to G substitution at nucleotide position 766, causing the methionine (M) at amino acid position 256 to be replaced by a valine (V). 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

0.083

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.017

.;T

Eigen

Benign

0.030

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.7

.;M

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.13

Sift

Benign

0.37

T;T

Sift4G

Benign

0.45

T;T

Polyphen

0.019

B;P

Vest4

0.31

MVP

0.71

MPC

0.17

ClinPred

0.17

GERP RS

5.4

Varity_R

0.33

gMVP

0.47

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