rs397515510
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PM4_Supporting
The NM_000095.3(COMP):c.1156_1158delAAC(p.Asn386del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: not found (cov: 31)
Consequence
COMP
NM_000095.3 conservative_inframe_deletion
NM_000095.3 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.88
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 region_of_interest Disordered (size 205) in uniprot entity COMP_HUMAN there are 109 pathogenic changes around while only 1 benign (99%) in NM_000095.3
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000095.3. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| COMP | ENST00000222271.7 | c.1156_1158delAAC | p.Asn386del | conservative_inframe_deletion | 11/19 | 1 | NM_000095.3 | ENSP00000222271.2 | ||
| COMP | ENST00000542601.6 | c.1057_1059delAAC | p.Asn353del | conservative_inframe_deletion | 10/18 | 1 | ENSP00000439156.2 | |||
| COMP | ENST00000425807.1 | c.997_999delAAC | p.Asn333del | conservative_inframe_deletion | 10/18 | 2 | ENSP00000403792.1 | |||
| COMP | ENST00000612179.1 | n.406_408delAAC | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
Multiple epiphyseal dysplasia Other:1
| not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at