5-5297087-A-T

Variant names:

• chr5-5297087-A-T
• rs16875288
• NM_139056.4:c.2790-6181A>T

Variant summary

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

The NM_139056.4(ADAMTS16):​c.2790-6181A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,096 control chromosomes in the GnomAD database, including 3,684 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3684 hom., cov: 33)
• Consequence: ADAMTS16 NM_139056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42
• Publications: 3 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]

LOC101929200 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

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.2790-6181A>T		intron	N/A	NP_620687.2	Q8TE57-1
	ADAMTS16	NR_136935.2		n.2797-6181A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS16	ENST00000274181.7	TSL:2 MANE Select	c.2790-6181A>T		intron	N/A	ENSP00000274181.7	Q8TE57-1
	ADAMTS16	ENST00000433402.2	TSL:1	n.2790-6181A>T		intron	N/A
	ADAMTS16	ENST00000918351.1		c.2652-6181A>T		intron	N/A	ENSP00000588410.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32882 AN: 151978 Hom.: 3685 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.209

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.216 AC: 32890 AN: 152096 Hom.: 3684 Cov.: 33 AF XY: 0.218 AC XY: 16217 AN XY: 74338

African (AFR) AF: 0.232 AC: 9613 AN: 41470

American (AMR) AF: 0.175 AC: 2677 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 813 AN: 3472

East Asian (EAS) AF: 0.228 AC: 1177 AN: 5164

South Asian (SAS) AF: 0.288 AC: 1389 AN: 4824

European-Finnish (FIN) AF: 0.227 AC: 2397 AN: 10580

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14113 AN: 67994

Other (OTH) AF: 0.207 AC: 436 AN: 2110

Alfa AF: 0.215 Hom.: 456

Bravo AF: 0.212

Asia WGS AF: 0.247 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.20
DANN	Benign	0.73
PhyloP100		-2.4
Mutation Taster		=100/0	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: rs16875288; hg19: chr5-5297200;