rs773713291
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_005120.3(MED12):c.5585G>A(p.Arg1862His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000546 in 1,098,211 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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. R1862C) has been classified as Uncertain significance.
Frequency
Consequence
NM_005120.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED12 | NM_005120.3 | c.5585G>A | p.Arg1862His | missense_variant | 39/45 | ENST00000374080.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED12 | ENST00000374080.8 | c.5585G>A | p.Arg1862His | missense_variant | 39/45 | 1 | NM_005120.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 111894Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34060 FAILED QC
GnomAD3 exomes AF: 0.0000166 AC: 3AN: 180566Hom.: 0 AF XY: 0.0000149 AC XY: 1AN XY: 67040
GnomAD4 exome AF: 0.00000546 AC: 6AN: 1098211Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 1AN XY: 363565
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 111894Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34060
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 04, 2022 | The p.R1862H variant (also known as c.5585G>A), located in coding exon 39 of the MED12 gene, results from a G to A substitution at nucleotide position 5585. The arginine at codon 1862 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
FG syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2023 | 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MED12 protein function. ClinVar contains an entry for this variant (Variation ID: 458820). This variant has not been reported in the literature in individuals affected with MED12-related conditions. This variant is present in population databases (rs773713291, gnomAD 0.008%), including at least one homozygous and/or hemizygous individual. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1862 of the MED12 protein (p.Arg1862His). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at