rs6766801

Positions:

• chr3-64516022-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000498707.5(ADAMTS9):​c.*1105A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 152,346 control chromosomes in the GnomAD database, including 57 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 0.011 (57 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAMTS9 ENST00000498707.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS9	NM_182920.2	c.*1105A>G		3_prime_UTR_variant	40/40	ENST00000498707.5	NP_891550.1
ADAMTS9	NM_001318781.2	c.*1105A>G		3_prime_UTR_variant	39/39		NP_001305710.1
ADAMTS9	XR_007095711.1	n.7355A>G		non_coding_transcript_exon_variant	40/40
ADAMTS9	XR_245151.1	n.7439A>G		non_coding_transcript_exon_variant	41/41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS9	ENST00000498707.5	c.*1105A>G		3_prime_UTR_variant	40/40	1	NM_182920.2	ENSP00000418735	P1
ADAMTS9	ENST00000295903.8	c.*1105A>G		3_prime_UTR_variant	39/39	1		ENSP00000295903
ADAMTS9	ENST00000477180.1	n.1446A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1593 AN: 152228 Hom.: 54 Cov.: 32

Gnomad AFR AF: 0.00350

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0497

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.0679

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.00555

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000808

Gnomad OTH AF: 0.0163

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0106 AC: 1614 AN: 152346 Hom.: 57 Cov.: 32 AF XY: 0.0124 AC XY: 921 AN XY: 74508

Gnomad4 AFR AF: 0.00356

Gnomad4 AMR AF: 0.0504

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.0682

Gnomad4 SAS AF: 0.0364

Gnomad4 FIN AF: 0.00555

Gnomad4 NFE AF: 0.000808

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.00598 Hom.: 23

Bravo AF: 0.0146

Asia WGS AF: 0.0660 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.49

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: rs6766801; hg19: chr3-64501698;