rs374403178
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_004830.4(MED23):c.367C>T(p.Arg123Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,613,598 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. R123Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_004830.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED23 | NM_004830.4 | c.367C>T | p.Arg123Trp | missense_variant | 5/29 | ENST00000368068.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED23 | ENST00000368068.8 | c.367C>T | p.Arg123Trp | missense_variant | 5/29 | 1 | NM_004830.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 151930Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251436Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135900
GnomAD4 exome AF: 0.0000499 AC: 73AN: 1461668Hom.: 0 Cov.: 31 AF XY: 0.0000564 AC XY: 41AN XY: 727160
GnomAD4 genome ? AF: 0.0000658 AC: 10AN: 151930Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74174
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 15, 2020 | The p.R123W variant (also known as c.367C>T), located in coding exon 5 of the MED23 gene, results from a C to T substitution at nucleotide position 367. The arginine at codon 123 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Intellectual disability, autosomal recessive 18 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 10, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at