5-5146208-G-T

Variant names:

• chr5-5146208-G-T
• rs368411395
• NM_139056.4:c.254G>T

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ADAMTS16 NM_139056.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS16	NM_139056.4	c.254G>T	p.Arg85Leu	missense_variant	Exon 3 of 23	ENST00000274181.7	NP_620687.2
ADAMTS16	XM_047416874.1	c.254G>T	p.Arg85Leu	missense_variant	Exon 3 of 22		XP_047272830.1
ADAMTS16	XM_047416875.1	c.254G>T	p.Arg85Leu	missense_variant	Exon 3 of 20		XP_047272831.1
ADAMTS16	NR_136935.2	n.392G>T		non_coding_transcript_exon_variant	Exon 3 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS16	ENST00000274181.7	c.254G>T	p.Arg85Leu	missense_variant	Exon 3 of 23	2	NM_139056.4	ENSP00000274181.7
ADAMTS16	ENST00000511368.5	c.254G>T	p.Arg85Leu	missense_variant	Exon 3 of 11	1		ENSP00000421631.1
ADAMTS16	ENST00000433402.2	n.254G>T		non_coding_transcript_exon_variant	Exon 3 of 20	1
ENSG00000250866	ENST00000514848.1	n.221-3837C>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	.;T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0096	T
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	2.9	.;M
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.20
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.93	P;D
Vest4		0.49
MutPred		0.52		Loss of disorder (P = 0.0231);Loss of disorder (P = 0.0231);
MVP		0.66
MPC		0.52
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.34
gMVP		0.71

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

Other links and lift over

dbSNP: rs368411395; hg19: chr5-5146321; COSMIC: COSV57001579;