2-188974503-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP2PP3
The NM_000090.4(COL3A1):c.14T>A(p.Val5Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000090.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL3A1 | ENST00000304636.9 | c.14T>A | p.Val5Glu | missense_variant | Exon 1 of 51 | 1 | NM_000090.4 | ENSP00000304408.4 | ||
COL3A1 | ENST00000450867.2 | c.14T>A | p.Val5Glu | missense_variant | Exon 1 of 50 | 1 | ENSP00000415346.2 | |||
COL3A1 | ENST00000470167.1 | n.110T>A | non_coding_transcript_exon_variant | Exon 1 of 2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251380Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135870
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461770Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 727188
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74338
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, type 4 Uncertain:2
This missense variant replaces valine with glutamic acid at codon 5 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 COL3A1-related disorders in the literature. This variant has been identified in 3/251380 chromosomes 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. -
This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 5 of the COL3A1 protein (p.Val5Glu). This variant is present in population databases (rs751315184, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1400615). 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. 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. -
not provided Uncertain:1
COL3A1: PM2 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at