rs1057519250
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM1PP2BP4
The NM_000090.4(COL3A1):c.1235C>A(p.Ala412Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A412S) has been classified as Likely benign.
Frequency
Consequence
NM_000090.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL3A1 | NM_000090.4 | c.1235C>A | p.Ala412Asp | missense_variant | 18/51 | ENST00000304636.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL3A1 | ENST00000304636.9 | c.1235C>A | p.Ala412Asp | missense_variant | 18/51 | 1 | NM_000090.4 | P1 | |
COL3A1 | ENST00000450867.2 | c.1136C>A | p.Ala379Asp | missense_variant | 17/50 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251096Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135706
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461654Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727146
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74324
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 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: 1015656). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.008%). This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 412 of the COL3A1 protein (p.Ala412Asp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at