Variant 5-5140692-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_139056.4(ADAMTS16):c.101C>T(p.Ala34Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,410,616 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: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ADAMTS16
NM_139056.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.722

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 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=0.24250391).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADAMTS16	NM_139056.4 linkuse as main transcript	c.101C>T	p.Ala34Val	missense_variant	2/23	ENST00000274181.7	NP_620687.2
ADAMTS16	XM_047416874.1 linkuse as main transcript	c.101C>T	p.Ala34Val	missense_variant	2/22		XP_047272830.1
ADAMTS16	XM_047416875.1 linkuse as main transcript	c.101C>T	p.Ala34Val	missense_variant	2/20		XP_047272831.1
ADAMTS16	NR_136935.2 linkuse as main transcript	n.239C>T		non_coding_transcript_exon_variant	2/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS16	ENST00000274181.7 linkuse as main transcript	c.101C>T	p.Ala34Val	missense_variant	2/23	2	NM_139056.4	ENSP00000274181	P1	Q8TE57-1
ADAMTS16	ENST00000511368.5 linkuse as main transcript	c.101C>T	p.Ala34Val	missense_variant	2/11	1		ENSP00000421631
ADAMTS16	ENST00000433402.2 linkuse as main transcript	n.101C>T		non_coding_transcript_exon_variant	2/20	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000213

AC:

AN:

1410616

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

697364

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.18e-7

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Nov 09, 2023

The c.101C>T (p.A34V) alteration is located in exon 2 (coding exon 2) of the ADAMTS16 gene. This alteration results from a C to T substitution at nucleotide position 101, causing the alanine (A) at amino acid position 34 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

0.16

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

.;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.046

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.0

.;L

MutationTaster

Benign

0.86

N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.83

N;N

REVEL

Benign

0.16

Sift

Benign

0.21

T;T

Sift4G

Uncertain

0.011

D;D

Polyphen

0.97

D;D

Vest4

0.34

MutPred

0.44

Gain of catalytic residue at A34 (P = 0.0054);Gain of catalytic residue at A34 (P = 0.0054);

MVP

0.65

MPC

0.19

ClinPred

0.64

GERP RS

4.0

Varity_R

0.11

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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