rs1553508711
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PP2PP5
The NM_000090.4(COL3A1):c.2264C>A(p.Pro755Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,593,608 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P755P) has been classified as Likely benign.
Frequency
Consequence
NM_000090.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL3A1 | NM_000090.4 | c.2264C>A | p.Pro755Gln | missense_variant | 32/51 | ENST00000304636.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL3A1 | ENST00000304636.9 | c.2264C>A | p.Pro755Gln | missense_variant | 32/51 | 1 | NM_000090.4 | P1 | |
COL3A1 | ENST00000450867.2 | c.2165C>A | p.Pro722Gln | missense_variant | 31/50 | 1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152098Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000194 AC: 28AN: 1441510Hom.: 0 Cov.: 32 AF XY: 0.0000154 AC XY: 11AN XY: 714538
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152098Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74298
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, type 4 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL3A1 protein function. ClinVar contains an entry for this variant (Variation ID: 529325). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 755 of the COL3A1 protein (p.Pro755Gln). - |
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Oct 23, 2023 | This missense variant replaces proline with glutamine at codon 755 of the COL3A1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory of Medical Genetics, National & Kapodistrian University of Athens | Mar 28, 2022 | PM1, PM2, PP2, PP3 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at