rs61757480
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_014243.3(ADAMTS3):āc.872T>Cā(p.Ile291Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000068 ( 0 hom. )
Consequence
ADAMTS3
NM_014243.3 missense
NM_014243.3 missense
Scores
11
5
2
Clinical Significance
Conservation
PhyloP100: 8.75
Genes affected
ADAMTS3 (HGNC:219): (ADAM metallopeptidase with thrombospondin type 1 motif 3) 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. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease, a member of the procollagen aminopropeptidase subfamily of proteins, may play a role in the processing of type II fibrillar collagen in articular cartilage. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.944
PP5
?
Variant 4-72323087-A-G is Pathogenic according to our data. Variant chr4-72323087-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 586988.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS3 | NM_014243.3 | c.872T>C | p.Ile291Thr | missense_variant | 6/22 | ENST00000286657.10 | |
ADAMTS3 | XM_011532421.2 | c.815T>C | p.Ile272Thr | missense_variant | 6/22 | ||
ADAMTS3 | XM_011532422.4 | c.788T>C | p.Ile263Thr | missense_variant | 6/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS3 | ENST00000286657.10 | c.872T>C | p.Ile291Thr | missense_variant | 6/22 | 1 | NM_014243.3 | P1 | |
ENST00000503918.1 | n.60A>G | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460706Hom.: 0 Cov.: 29 AF XY: 0.00000963 AC XY: 7AN XY: 726716
GnomAD4 exome
AF:
AC:
10
AN:
1460706
Hom.:
Cov.:
29
AF XY:
AC XY:
7
AN XY:
726716
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hennekam lymphangiectasia-lymphedema syndrome 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 10, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;.
REVEL
Pathogenic
Sift
Uncertain
D;.
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of stability (P = 0.0041);Loss of stability (P = 0.0041);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at