5-5260790-G-T

Variant names:

• chr5-5260790-G-T
• rs4323203
• NM_139056.4:c.2663-1867G>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.2663-1867G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,086 control chromosomes in the GnomAD database, including 45,802 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 0.76 (45802 hom., cov: 33)
• Consequence: ADAMTS16 NM_139056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 0 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.879 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS16	NM_139056.4	MANE Select	c.2663-1867G>T		intron	N/A	NP_620687.2
	ADAMTS16	NR_136935.2		n.2670-1867G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS16	ENST00000274181.7	TSL:2 MANE Select	c.2663-1867G>T		intron	N/A	ENSP00000274181.7
	ADAMTS16	ENST00000433402.2	TSL:1	n.2663-1867G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115872 AN: 151968 Hom.: 45798 Cov.: 33

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.794

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

GnomAD4 genome AF: 0.762 AC: 115920 AN: 152086 Hom.: 45802 Cov.: 33 AF XY: 0.758 AC XY: 56387 AN XY: 74364

African (AFR) AF: 0.575 AC: 23818 AN: 41450

American (AMR) AF: 0.680 AC: 10382 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2881 AN: 3472

East Asian (EAS) AF: 0.505 AC: 2601 AN: 5148

South Asian (SAS) AF: 0.793 AC: 3825 AN: 4822

European-Finnish (FIN) AF: 0.891 AC: 9447 AN: 10600

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.885 AC: 60215 AN: 68014

Other (OTH) AF: 0.791 AC: 1663 AN: 2102

Alfa AF: 0.831 Hom.: 159369

Bravo AF: 0.737

Asia WGS AF: 0.611 AC: 2126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.36
DANN	Benign	0.61
PhyloP100		-1.4
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: rs4323203; hg19: chr5-5260903;