chr16-77284060-A-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_199355.4(ADAMTS18):c.3562T>A(p.Cys1188Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000096 in 1,458,368 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. C1188C) 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 Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS18 | NM_199355.4 | c.3562T>A | p.Cys1188Ser | missense_variant | 23/23 | ENST00000282849.10 | |
ADAMTS18 | NM_001326358.2 | c.3046T>A | p.Cys1016Ser | missense_variant | 23/23 | ||
ADAMTS18 | XM_047433672.1 | c.2833T>A | p.Cys945Ser | missense_variant | 19/19 | ||
ADAMTS18 | XM_047433673.1 | c.2326T>A | p.Cys776Ser | missense_variant | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS18 | ENST00000282849.10 | c.3562T>A | p.Cys1188Ser | missense_variant | 23/23 | 1 | NM_199355.4 | P1 | |
ENST00000561672.1 | n.74-5216A>T | intron_variant, non_coding_transcript_variant | 2 | ||||||
ADAMTS18 | ENST00000562332.1 | c.96+5204T>A | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250726Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135476
GnomAD4 exome AF: 0.00000960 AC: 14AN: 1458368Hom.: 0 Cov.: 29 AF XY: 0.0000138 AC XY: 10AN XY: 725780
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 1188 of the ADAMTS18 protein (p.Cys1188Ser). This variant is present in population databases (rs761150429, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ADAMTS18-related conditions. ClinVar contains an entry for this variant (Variation ID: 954545). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at