rs4410439

chr3-64670048-A-Cchr3-64670048-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS9	NM_182920.2	c.679+11153T>G		intron_variant		ENST00000498707.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS9	ENST00000498707.5	c.679+11153T>G		intron_variant		1	NM_182920.2	P1

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

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.698

Alfa AF: 0.653 Hom.: 17984

Bravo AF: 0.715

Asia WGS AF: 0.665 AC: 2312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.0
Dann	Benign	0.33

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: rs4410439; hg19: chr3-64655724;