chr10-88935245-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PP2PP3_Strong
The NM_001613.4(ACTA2):c.1112T>C(p.Ile371Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,522 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I371N) has been classified as Uncertain significance.
Frequency
Consequence
NM_001613.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTA2 | NM_001613.4 | c.1112T>C | p.Ile371Thr | missense_variant | 9/9 | ENST00000224784.10 | |
ACTA2-AS1 | NR_125373.1 | n.870A>G | non_coding_transcript_exon_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTA2 | ENST00000224784.10 | c.1112T>C | p.Ile371Thr | missense_variant | 9/9 | 1 | NM_001613.4 | P1 | |
ACTA2-AS1 | ENST00000437930.4 | n.911A>G | non_coding_transcript_exon_variant | 3/5 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251272Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135790
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461336Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 726984
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2019 | - - |
Aortic aneurysm, familial thoracic 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2021 | 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 expected to disrupt ACTA2 protein function. ClinVar contains an entry for this variant (Variation ID: 806544). This variant has not been reported in the literature in individuals affected with ACTA2-related conditions. This variant is present in population databases (rs778887472, ExAC 0.01%). This sequence change replaces isoleucine with threonine at codon 371 of the ACTA2 protein (p.Ile371Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. 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