2-188995776-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM1PP2BP4_Strong
The NM_000090.4(COL3A1):c.1594G>A(p.Gly532Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000384 in 1,561,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G532D) has been classified as Uncertain significance.
Frequency
Consequence
NM_000090.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL3A1 | NM_000090.4 | c.1594G>A | p.Gly532Ser | missense_variant | 22/51 | ENST00000304636.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL3A1 | ENST00000304636.9 | c.1594G>A | p.Gly532Ser | missense_variant | 22/51 | 1 | NM_000090.4 | P1 | |
COL3A1 | ENST00000450867.2 | c.1495G>A | p.Gly499Ser | missense_variant | 21/50 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152094Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000596 AC: 1AN: 167762Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 88590
GnomAD4 exome AF: 0.00000284 AC: 4AN: 1409320Hom.: 0 Cov.: 30 AF XY: 0.00000431 AC XY: 3AN XY: 695994
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152094Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74278
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, type 4;C5193040:Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 20, 2021 | - - |
Ehlers-Danlos syndrome, type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 532 of the COL3A1 protein (p.Gly532Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 571343). 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 with a negative predictive value of 95%. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at