Genetic Variant ADAMTS16:p.Arg85Leu (chr5-5146208-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_139056.4(ADAMTS16):c.254G>T(p.Arg85Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R85Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Consequence

ADAMTS16
NM_139056.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.99

Publications

1 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-AS1 (HGNC:58093):

ADAMTS16-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAMTS16	NM_139056.4	MANE Select	c.254G>T	p.Arg85Leu	missense	Exon 3 of 23	NP_620687.2	Q8TE57-1
ADAMTS16	NR_136935.2		n.392G>T		non_coding_transcript_exon	Exon 3 of 22
ADAMTS16-AS1	NR_198969.1		n.221-3837C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAMTS16	ENST00000274181.7	TSL:2 MANE Select	c.254G>T	p.Arg85Leu	missense	Exon 3 of 23	ENSP00000274181.7	Q8TE57-1
ADAMTS16	ENST00000511368.5	TSL:1	c.254G>T	p.Arg85Leu	missense	Exon 3 of 11	ENSP00000421631.1	Q2XQZ0
ADAMTS16	ENST00000433402.2	TSL:1	n.254G>T		non_coding_transcript_exon	Exon 3 of 20

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

249500

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.76

M_CAP

Benign

0.0096

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

2.9

PhyloP100

3.0

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.20

Sift

Uncertain

0.012

Sift4G

Uncertain

0.0080

Polyphen

0.93

Vest4

0.49

MutPred

0.52

Loss of disorder (P = 0.0231)

MVP

0.66

MPC

0.52

ClinPred

0.98

GERP RS

5.5

Varity_R

0.34

gMVP

0.71

Mutation Taster

=80/20

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

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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