Genetic Variant ADAMTS9:c.679+11153T>G (chr3-64670048-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.213

Publications

4 publications found

Variant links:

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

ADAMTS9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS9	NM_182920.2 link	c.679+11153T>G		intron_variant	Intron 3 of 39	ENST00000498707.5	NP_891550.1	Q9P2N4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS9	ENST00000498707.5 link	c.679+11153T>G		intron_variant	Intron 3 of 39	1	NM_182920.2	ENSP00000418735.1		Q9P2N4-3

Frequencies

GnomAD3 genomes

AF:

0.698

AC:

106038

AN:

151924

Hom.:

38032

Cov.:

show subpopulations

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.:

AF XY:

0.691

AC XY:

51309

AN XY:

74282

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1563

3126

4690

6253

7816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

2.0

(source)

DANN

Benign

0.33

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over