3-64522185-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182920.2(ADAMTS9):​c.5794G>A​(p.Val1932Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ADAMTS9
NM_182920.2 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADAMTS9NM_182920.2 linkc.5794G>A p.Val1932Met missense_variant Exon 39 of 40 ENST00000498707.5 NP_891550.1 Q9P2N4-3
ADAMTS9NM_001318781.2 linkc.5710G>A p.Val1904Met missense_variant Exon 38 of 39 NP_001305710.1 Q9P2N4-4
ADAMTS9XR_007095711.1 linkn.6053G>A non_coding_transcript_exon_variant Exon 38 of 40
ADAMTS9XR_245151.1 linkn.6137G>A non_coding_transcript_exon_variant Exon 39 of 41

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADAMTS9ENST00000498707.5 linkc.5794G>A p.Val1932Met missense_variant Exon 39 of 40 1 NM_182920.2 ENSP00000418735.1 Q9P2N4-3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.5794G>A (p.V1932M) alteration is located in exon 39 (coding exon 39) of the ADAMTS9 gene. This alteration results from a G to A substitution at nucleotide position 5794, causing the valine (V) at amino acid position 1932 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.093
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;.
Eigen
Benign
0.15
Eigen_PC
Benign
0.15
FATHMM_MKL
Benign
0.73
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.47
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.19
Sift
Uncertain
0.0080
D;D
Sift4G
Uncertain
0.0070
D;D
Polyphen
0.59
P;.
Vest4
0.49
MutPred
0.41
Loss of sheet (P = 0.1158);.;
MVP
0.52
MPC
0.64
ClinPred
0.89
D
GERP RS
3.9
Varity_R
0.091
gMVP
0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-64507861; API