rs2086310

Variant names:

• chr5-5146222-C-G
• rs2086310
• NM_139056.4:c.268C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139056.4(ADAMTS16):​c.268C>G​(p.Pro90Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 1,613,920 control chromosomes in the GnomAD database, including 512,423 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.75 (43634 hom., cov: 32)
  • Exomes 𝑓: 0.80 (468789 hom.)
• Consequence: ADAMTS16 NM_139056.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• Publications: 28 publications found

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]

ENSG00000250866 (HGNC:58093):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0635891E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS16	NM_139056.4	c.268C>G	p.Pro90Ala	missense_variant	Exon 3 of 23	ENST00000274181.7	NP_620687.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS16	ENST00000274181.7	c.268C>G	p.Pro90Ala	missense_variant	Exon 3 of 23	2	NM_139056.4	ENSP00000274181.7
ADAMTS16	ENST00000511368.5	c.268C>G	p.Pro90Ala	missense_variant	Exon 3 of 11	1		ENSP00000421631.1
ADAMTS16	ENST00000433402.2	n.268C>G		non_coding_transcript_exon_variant	Exon 3 of 20	1
ENSG00000250866	ENST00000514848.1	n.221-3851G>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114281 AN: 151956 Hom.: 43608 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.922

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.774

GnomAD2 exomes AF: 0.784 AC: 195563 AN: 249488 AF XY: 0.788

Gnomad AFR exome AF: 0.619

Gnomad AMR exome AF: 0.888

Gnomad ASJ exome AF: 0.916

Gnomad EAS exome AF: 0.508

Gnomad FIN exome AF: 0.750

Gnomad NFE exome AF: 0.799

Gnomad OTH exome AF: 0.813

GnomAD4 exome AF: 0.798 AC: 1166421 AN: 1461846 Hom.: 468789 Cov.: 66 AF XY: 0.800 AC XY: 581510 AN XY: 727226

African (AFR) AF: 0.617 AC: 20644 AN: 33480

American (AMR) AF: 0.885 AC: 39562 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 24051 AN: 26136

East Asian (EAS) AF: 0.517 AC: 20529 AN: 39698

South Asian (SAS) AF: 0.827 AC: 71351 AN: 86258

European-Finnish (FIN) AF: 0.752 AC: 40183 AN: 53404

Middle Eastern (MID) AF: 0.891 AC: 5138 AN: 5768

European-Non Finnish (NFE) AF: 0.806 AC: 896702 AN: 1111982

Other (OTH) AF: 0.799 AC: 48261 AN: 60396

GnomAD4 genome AF: 0.752 AC: 114347 AN: 152074 Hom.: 43634 Cov.: 32 AF XY: 0.750 AC XY: 55711 AN XY: 74324

African (AFR) AF: 0.632 AC: 26189 AN: 41434

American (AMR) AF: 0.849 AC: 12977 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.922 AC: 3202 AN: 3472

East Asian (EAS) AF: 0.522 AC: 2682 AN: 5142

South Asian (SAS) AF: 0.815 AC: 3925 AN: 4816

European-Finnish (FIN) AF: 0.757 AC: 8011 AN: 10586

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.805 AC: 54784 AN: 68014

Other (OTH) AF: 0.768 AC: 1622 AN: 2112

Alfa AF: 0.800 Hom.: 37074

Bravo AF: 0.752

TwinsUK AF: 0.802 AC: 2975

ALSPAC AF: 0.795 AC: 3065

ESP6500AA AF: 0.644 AC: 2623

ESP6500EA AF: 0.816 AC: 6831

ExAC AF: 0.775 AC: 93746

Asia WGS AF: 0.642 AC: 2236 AN: 3478

EpiCase AF: 0.816

EpiControl AF: 0.824

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.058
DANN	Benign	0.38
DEOGEN2	Benign	0.0052	.;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.14	T;T
MetaRNN	Benign	0.0000011	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.4	.;N
PhyloP100		-0.40
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.71	N;N
REVEL	Benign	0.012
Sift	Benign	1.0	T;T
Sift4G	Benign	0.80	T;T
Polyphen		0.0	B;B
Vest4		0.018
MPC		0.16
ClinPred		0.00030	T
GERP RS		-0.85
Varity_R		0.035
gMVP		0.12
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2086310; hg19: chr5-5146335; COSMIC: COSV56986942;