16-77434499-G-A
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_199355.4(ADAMTS18):c.97C>T(p.Gln33Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000071 in 1,408,260 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 𝑓: 7.1e-7 ( 0 hom. )
Consequence
ADAMTS18
NM_199355.4 stop_gained
NM_199355.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 6.99
Genes affected
ADAMTS18 (HGNC:17110): (ADAM metallopeptidase with thrombospondin type 1 motif 18) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS family members 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 protein, which may regulate hemostatic balance and function as a tumor suppressor. Mutations in this gene may be associated with microcornea, myopic chorioretinal atrophy, and telecanthus (MMCAT) and cone-rod dystrophy in human patients. [provided by RefSeq, May 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 36 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 16-77434499-G-A is Pathogenic according to our data. Variant chr16-77434499-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 66042.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-77434499-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS18 | NM_199355.4 | c.97C>T | p.Gln33Ter | stop_gained | 2/23 | ENST00000282849.10 | |
ADAMTS18 | NM_001326358.2 | c.-424C>T | 5_prime_UTR_variant | 2/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS18 | ENST00000282849.10 | c.97C>T | p.Gln33Ter | stop_gained | 2/23 | 1 | NM_199355.4 | P1 | |
ADAMTS18 | ENST00000564369.1 | n.23C>T | non_coding_transcript_exon_variant | 1/3 | 4 | ||||
ADAMTS18 | ENST00000449265.2 | c.97C>T | p.Gln33Ter | stop_gained, NMD_transcript_variant | 2/8 | 2 | |||
ENST00000564358.1 | n.87+1031G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 7.10e-7 AC: 1AN: 1408260Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 696630
GnomAD4 exome
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31
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Microcornea-myopic chorioretinal atrophy Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at