Genetic Variant ADAMTS16:p.Pro52Gln (chr5-5140746-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139056.4(ADAMTS16):c.155C>A(p.Pro52Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P52R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ADAMTS16
NM_139056.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.185

Publications

0 publications found

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:

ADAMTS16-DT (HGNC:55548): (ADAMTS16 divergent transcript)

ADAMTS16-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.086856455).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139056.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS16	NM_139056.4	MANE Select	c.155C>A	p.Pro52Gln	missense	Exon 2 of 23	NP_620687.2	Q8TE57-1
	ADAMTS16	NR_136935.2		n.293C>A		non_coding_transcript_exon	Exon 2 of 22

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAMTS16	ENST00000274181.7	TSL:2 MANE Select	c.155C>A	p.Pro52Gln	missense	Exon 2 of 23	ENSP00000274181.7	Q8TE57-1
ADAMTS16	ENST00000511368.5	TSL:1	c.155C>A	p.Pro52Gln	missense	Exon 2 of 11	ENSP00000421631.1	Q2XQZ0
ADAMTS16	ENST00000433402.2	TSL:1	n.155C>A		non_coding_transcript_exon	Exon 2 of 20

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000586

AC:

AN:

170700

AF XY:

0.0000108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000740

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1414020

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

699040

African (AFR)

AF:

0.00

AC:

AN:

32396

American (AMR)

AF:

0.00

AC:

AN:

37962

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25244

East Asian (EAS)

AF:

0.00

AC:

AN:

37940

South Asian (SAS)

AF:

0.00

AC:

AN:

80648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5626

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1088912

Other (OTH)

AF:

0.00

AC:

AN:

58704

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.017

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.46

M_CAP

Benign

0.013

MetaRNN

Benign

0.087

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

-0.18

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.30

REVEL

Benign

0.050

Sift

Benign

0.69

Sift4G

Benign

0.096

Polyphen

0.31

Vest4

0.31

MutPred

0.33

Loss of glycosylation at P52 (P = 0.0544)

MVP

0.50

MPC

0.18

ClinPred

0.069

GERP RS

-1.5

PromoterAI

-0.019

Neutral

(source)

Varity_R

0.051

gMVP

0.30

Mutation Taster

=81/19

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over