X-71118853-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_005120.3(MED12):c.99G>A(p.Glu33=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00000274 in 1,094,709 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005120.3 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED12 | NM_005120.3 | c.99G>A | p.Glu33= | splice_region_variant, synonymous_variant | 1/45 | ENST00000374080.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED12 | ENST00000374080.8 | c.99G>A | p.Glu33= | splice_region_variant, synonymous_variant | 1/45 | 1 | NM_005120.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 20
GnomAD4 exome AF: 0.00000274 AC: 3AN: 1094709Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 360247
GnomAD4 genome ? Cov.: 20
ClinVar
Submissions by phenotype
FG syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2023 | This sequence change affects codon 33 of the MED12 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MED12 protein. This variant also falls at the last nucleotide of exon 1, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MED12-related conditions. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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
Publications
No publications associated with this variant yet.