rs1553507557
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PP2PP3_StrongPP5_Moderate
The NM_000090.4(COL3A1):c.889G>A(p.Gly297Arg) 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. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G297G) has been classified as Likely benign.
Frequency
Consequence
NM_000090.4 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 |
---|---|---|---|---|---|---|---|
COL3A1 | NM_000090.4 | c.889G>A | p.Gly297Arg | missense_variant | 12/51 | ENST00000304636.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL3A1 | ENST00000304636.9 | c.889G>A | p.Gly297Arg | missense_variant | 12/51 | 1 | NM_000090.4 | P1 | |
COL3A1 | ENST00000450867.2 | c.889G>A | p.Gly297Arg | missense_variant | 12/50 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, type 4 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2003 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 06, 2019 | Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL3A1, variants that affect these glycine residues are significantly enriched in individuals with disease (PMID: 24922459, 25758994) compared to the general population (ExAC). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has been observed in a family affected with Ehlers Danlos syndrome (PMID: 12694234). This variant is also known as Gly130Arg in the literature. ClinVar contains an entry for this variant (Variation ID: 17229). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 297 of the COL3A1 protein (p.Gly297Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at