5-5140481-C-T

Position:

chr5-5140481-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_139056.4(ADAMTS16):c.14C>T(p.Ala5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,515,346 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 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

ADAMTS16
NM_139056.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.19

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=0.044125468).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADAMTS16	NM_139056.4 linkuse as main transcript	c.14C>T	p.Ala5Val	missense_variant	1/23	ENST00000274181.7	NP_620687.2
ADAMTS16	XM_047416874.1 linkuse as main transcript	c.14C>T	p.Ala5Val	missense_variant	1/22		XP_047272830.1
ADAMTS16	XM_047416875.1 linkuse as main transcript	c.14C>T	p.Ala5Val	missense_variant	1/20		XP_047272831.1
ADAMTS16	NR_136935.2 linkuse as main transcript	n.152C>T		non_coding_transcript_exon_variant	1/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS16	ENST00000274181.7 linkuse as main transcript	c.14C>T	p.Ala5Val	missense_variant	1/23	2	NM_139056.4	ENSP00000274181	P1	Q8TE57-1
ADAMTS16	ENST00000511368.5 linkuse as main transcript	c.14C>T	p.Ala5Val	missense_variant	1/11	1		ENSP00000421631
ADAMTS16	ENST00000433402.2 linkuse as main transcript	n.14C>T		non_coding_transcript_exon_variant	1/20	1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000353

AC:

AN:

113264

Hom.:

AF XY:

0.0000313

AC XY:

AN XY:

63822

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000425

Gnomad SAS exome

AF:

0.0000482

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1363074

Hom.:

Cov.:

AF XY:

0.0000223

AC XY:

AN XY:

673214

show subpopulations

Gnomad4 AFR exome

AF:

0.0000709

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000556

Gnomad4 SAS exome

AF:

0.0000776

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000176

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000389

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

ExAC

AF:

0.00000969

AC:

Asia WGS

AF:

0.000579

AC:

AN:

3468

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

Dec 27, 2023

The c.14C>T (p.A5V) alteration is located in exon 1 (coding exon 1) of the ADAMTS16 gene. This alteration results from a C to T substitution at nucleotide position 14, causing the alanine (A) at amino acid position 5 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

0.22

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.30

DANN

Benign

0.97

DEOGEN2

Benign

0.0091

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0065

LIST_S2

Benign

0.46

T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.38

N;N

REVEL

Benign

0.068

Sift

Benign

0.039

D;D

Sift4G

Uncertain

0.051

T;T

Polyphen

0.0

B;B

Vest4

0.092

MutPred

0.33

Loss of disorder (P = 0.0436);Loss of disorder (P = 0.0436);

MVP

0.44

MPC

0.16

ClinPred

0.021

GERP RS

-3.6

Varity_R

0.031

gMVP

0.17

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