rs766267057

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030955.4(ADAMTS12):​c.4553C>T​(p.Pro1518Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1518R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ADAMTS12
NM_030955.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.903
Variant links:
Genes affected
ADAMTS12 (HGNC:14605): (ADAM metallopeptidase with thrombospondin type 1 motif 12) 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-1) motif. Individual members of this family differ in the number of C-terminal TS-1 motifs, and some have unique C-terminal domains. The enzyme encoded by this gene contains eight TS-1 motifs. It may play roles in pulmonary cells during fetal development or in tumor processes through its proteolytic activity or as a molecule potentially involved in regulation of cell adhesion. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.091103315).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADAMTS12NM_030955.4 linkc.4553C>T p.Pro1518Leu missense_variant Exon 23 of 24 ENST00000504830.6 NP_112217.2 P58397-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADAMTS12ENST00000504830.6 linkc.4553C>T p.Pro1518Leu missense_variant Exon 23 of 24 1 NM_030955.4 ENSP00000422554.1 P58397-1
ADAMTS12ENST00000352040.7 linkc.4298C>T p.Pro1433Leu missense_variant Exon 21 of 22 1 ENSP00000344847.3 P58397-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
17
DANN
Benign
0.93
DEOGEN2
Benign
0.062
T;.
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.091
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.56
N;.
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-2.2
N;N
REVEL
Benign
0.029
Sift
Benign
0.50
T;T
Sift4G
Benign
0.36
T;T
Polyphen
0.0010
B;B
Vest4
0.13
MutPred
0.20
Gain of catalytic residue at P1518 (P = 0.0433);.;
MVP
0.67
MPC
0.15
ClinPred
0.082
T
GERP RS
2.3
Varity_R
0.049
gMVP
0.31

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs766267057; hg19: chr5-33534991; API