rs387906972
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_199355.4(ADAMTS18):c.536C>T(p.Ser179Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S179S) has been classified as Likely benign.
Frequency
Consequence
NM_199355.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS18 | NM_199355.4 | c.536C>T | p.Ser179Leu | missense_variant | 4/23 | ENST00000282849.10 | |
ADAMTS18 | NM_001326358.2 | c.16C>T | p.Arg6Cys | missense_variant | 4/23 | ||
ADAMTS18 | XM_047433672.1 | c.16C>T | p.Arg6Cys | missense_variant | 1/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS18 | ENST00000282849.10 | c.536C>T | p.Ser179Leu | missense_variant | 4/23 | 1 | NM_199355.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152150Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251400Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135866
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461872Hom.: 0 Cov.: 34 AF XY: 0.0000261 AC XY: 19AN XY: 727242
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152150Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74344
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 10, 2022 | This sequence change replaces serine with leucine at codon 179 of the ADAMTS18 protein (p.Ser179Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 30670). This variant has not been reported in the literature in individuals affected with ADAMTS18-related conditions. This variant is present in population databases (rs387906972, gnomAD 0.02%). - |
Knobloch syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | OMIM | Aug 01, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at