16-77283988-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_199355.4(ADAMTS18):c.3634C>T(p.Gln1212Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,762 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. Q1212Q) has been classified as Likely benign.
Frequency
Consequence
NM_199355.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS18 | NM_199355.4 | c.3634C>T | p.Gln1212Ter | stop_gained | 23/23 | ENST00000282849.10 | |
ADAMTS18 | NM_001326358.2 | c.3118C>T | p.Gln1040Ter | stop_gained | 23/23 | ||
ADAMTS18 | XM_047433672.1 | c.2905C>T | p.Gln969Ter | stop_gained | 19/19 | ||
ADAMTS18 | XM_047433673.1 | c.2398C>T | p.Gln800Ter | stop_gained | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS18 | ENST00000282849.10 | c.3634C>T | p.Gln1212Ter | stop_gained | 23/23 | 1 | NM_199355.4 | P1 | |
ENST00000561672.1 | n.74-5288G>A | intron_variant, non_coding_transcript_variant | 2 | ||||||
ADAMTS18 | ENST00000562332.1 | c.96+5276C>T | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152032Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461730Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 727178
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152032Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74230
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2022 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1427881). This variant has not been reported in the literature in individuals affected with ADAMTS18-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1212*) in the ADAMTS18 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 10 amino acid(s) of the ADAMTS18 protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at