rs28936668
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP3_StrongPP5
The NM_000095.3(COMP):c.1358A>G(p.Asn453Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N453K) has been classified as Pathogenic.
Frequency
Consequence
NM_000095.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COMP | NM_000095.3 | c.1358A>G | p.Asn453Ser | missense_variant | 13/19 | ENST00000222271.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COMP | ENST00000222271.7 | c.1358A>G | p.Asn453Ser | missense_variant | 13/19 | 1 | NM_000095.3 | P1 | |
COMP | ENST00000542601.6 | c.1259A>G | p.Asn420Ser | missense_variant | 12/18 | 1 | |||
COMP | ENST00000425807.1 | c.1199A>G | p.Asn400Ser | missense_variant | 12/18 | 2 | |||
COMP | ENST00000612179.1 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 36
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Epiphyseal dysplasia, multiple, 1, severe Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 1998 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at