rs878854752
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_005120.3(MED12):c.2068A>G(p.Thr690Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000255 in 1,097,541 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005120.3 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 |
---|---|---|---|---|---|---|---|
MED12 | NM_005120.3 | c.2068A>G | p.Thr690Ala | missense_variant | 15/45 | ENST00000374080.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED12 | ENST00000374080.8 | c.2068A>G | p.Thr690Ala | missense_variant | 15/45 | 1 | NM_005120.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD4 exome AF: 0.0000255 AC: 28AN: 1097541Hom.: 0 Cov.: 33 AF XY: 0.0000358 AC XY: 13AN XY: 362903
GnomAD4 genome ? Cov.: 22
ClinVar
Submissions by phenotype
FG syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 10, 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) performed at Invitae indicates that this missense variant is not expected to disrupt MED12 protein function. ClinVar contains an entry for this variant (Variation ID: 240095). This variant has not been reported in the literature in individuals affected with MED12-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 690 of the MED12 protein (p.Thr690Ala). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at