3-64540037-T-A

Variant names:

• chr3-64540037-T-A
• rs9847307
• NM_182920.2:c.5522-743A>T

Variant summary

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

The NM_182920.2(ADAMTS9):​c.5522-743A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0727 in 152,290 control chromosomes in the GnomAD database, including 1,349 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 0.073 (1349 hom., cov: 33)
• Consequence: ADAMTS9 NM_182920.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.297 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS9	NM_182920.2	MANE Select	c.5522-743A>T		intron	N/A	NP_891550.1	Q9P2N4-3
	ADAMTS9	NM_001318781.2		c.5438-743A>T		intron	N/A	NP_001305710.1	Q9P2N4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS9	ENST00000498707.5	TSL:1 MANE Select	c.5522-743A>T		intron	N/A	ENSP00000418735.1	Q9P2N4-3
	ADAMTS9	ENST00000295903.8	TSL:1	c.5438-743A>T		intron	N/A	ENSP00000295903.4	Q9P2N4-4
	ADAMTS9	ENST00000481060.2	TSL:2	c.2687-743A>T		intron	N/A	ENSP00000417521.1	H0Y859

Frequencies

GnomAD3 genomes AF: 0.0725 AC: 11036 AN: 152170 Hom.: 1333 Cov.: 33

Gnomad AFR AF: 0.0927

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.0574

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00604

Gnomad OTH AF: 0.0781

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

GnomAD4 genome AF: 0.0727 AC: 11073 AN: 152290 Hom.: 1349 Cov.: 33 AF XY: 0.0779 AC XY: 5804 AN XY: 74466

African (AFR) AF: 0.0926 AC: 3849 AN: 41572

American (AMR) AF: 0.304 AC: 4655 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.288 AC: 1489 AN: 5164

South Asian (SAS) AF: 0.0574 AC: 277 AN: 4822

European-Finnish (FIN) AF: 0.0191 AC: 203 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00604 AC: 411 AN: 68026

Other (OTH) AF: 0.0791 AC: 167 AN: 2110

Alfa AF: 0.0382 Hom.: 93

Bravo AF: 0.101

Asia WGS AF: 0.167 AC: 580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.3
DANN	Benign	0.67
PhyloP100		2.0
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: rs9847307; hg19: chr3-64525713;