chr19-18786034-T-TGTCGTC
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP5
The NM_000095.3(COMP):c.1419_1420insGACGAC(p.Asp472_Asp473dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
COMP
NM_000095.3 inframe_insertion
NM_000095.3 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.28
Genes affected
COMP (HGNC:2227): (cartilage oligomeric matrix protein) The protein encoded by this gene is a noncollagenous extracellular matrix (ECM) protein. It consists of five identical glycoprotein subunits, each with EGF-like and calcium-binding (thrombospondin-like) domains. Oligomerization results from formation of a five-stranded coiled coil and disulfides. Binding to other ECM proteins such as collagen appears to depend on divalent cations. Contraction or expansion of a 5 aa aspartate repeat and other mutations can cause pseudochondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM1
?
In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 6 uncertain in NM_000095.3
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 19-18786034-T-TGTCGTC is Pathogenic according to our data. Variant chr19-18786034-T-TGTCGTC is described in ClinVar as [Pathogenic]. Clinvar id is 9192.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COMP | NM_000095.3 | c.1419_1420insGACGAC | p.Asp472_Asp473dup | inframe_insertion | 13/19 | ENST00000222271.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COMP | ENST00000222271.7 | c.1419_1420insGACGAC | p.Asp472_Asp473dup | inframe_insertion | 13/19 | 1 | NM_000095.3 | P1 | |
COMP | ENST00000542601.6 | c.1320_1321insGACGAC | p.Asp439_Asp440dup | inframe_insertion | 12/18 | 1 | |||
COMP | ENST00000425807.1 | c.1260_1261insGACGAC | p.Asp419_Asp420dup | inframe_insertion | 12/18 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 36
GnomAD4 exome
Cov.:
36
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
Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 1999 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at