NM_182920.2:c.679+11153T>G

Variant names:

• chr3-64670048-A-C
• rs4410439
• NM_182920.2:c.679+11153T>G

Variant summary

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

The NM_182920.2(ADAMTS9):​c.679+11153T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,042 control chromosomes in the GnomAD database, including 38,076 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 0.70 (38076 hom., cov: 31)
• Consequence: ADAMTS9 NM_182920.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• Publications: 4 publications found

Genes affected

ADAMTS9 (HGNC:13202): (ADAM metallopeptidase with thrombospondin type 1 motif 9) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family 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. Members of the ADAMTS family have been implicated in the cleavage of proteoglycans, the control of organ shape during development, and the inhibition of angiogenesis. This gene is localized to chromosome 3p14.3-p14.2, an area known to be lost in hereditary renal tumors. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Jan 2016]

ADAMTS9 Gene-Disease associations (from GenCC):

• nephronophthisis 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• ciliopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

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 (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182920.2. 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
	ADAMTS9	NM_182920.2	MANE Select	c.679+11153T>G		intron	N/A	NP_891550.1
	ADAMTS9	NM_001318781.2		c.679+11153T>G		intron	N/A	NP_001305710.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS9	ENST00000498707.5	TSL:1 MANE Select	c.679+11153T>G		intron	N/A	ENSP00000418735.1
	ADAMTS9	ENST00000295903.8	TSL:1	c.679+11153T>G		intron	N/A	ENSP00000295903.4
	ADAMTS9	ENST00000459780.1	TSL:1	c.679+11153T>G		intron	N/A	ENSP00000419217.1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106038 AN: 151924 Hom.: 38032 Cov.: 31

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.698 AC: 106138 AN: 152042 Hom.: 38076 Cov.: 31 AF XY: 0.691 AC XY: 51309 AN XY: 74282

African (AFR) AF: 0.877 AC: 36378 AN: 41482

American (AMR) AF: 0.653 AC: 9973 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2126 AN: 3466

East Asian (EAS) AF: 0.633 AC: 3269 AN: 5166

South Asian (SAS) AF: 0.619 AC: 2989 AN: 4826

European-Finnish (FIN) AF: 0.558 AC: 5890 AN: 10558

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43318 AN: 67952

Other (OTH) AF: 0.698 AC: 1473 AN: 2110

Alfa AF: 0.652 Hom.: 19621

Bravo AF: 0.715

Asia WGS AF: 0.665 AC: 2312 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	2.0
DANN	Benign	0.33
PhyloP100		-0.21
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: rs4410439; hg19: chr3-64655724;