rs1135401775
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PM5PP2PP3_Moderate
The NM_005120.3(MED12):c.2545T>C(p.Ser849Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S849F) has been classified as Likely pathogenic.
Frequency
Consequence
NM_005120.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED12 | NM_005120.3 | c.2545T>C | p.Ser849Pro | missense_variant | 19/45 | ENST00000374080.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED12 | ENST00000374080.8 | c.2545T>C | p.Ser849Pro | missense_variant | 19/45 | 1 | NM_005120.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
X-linked intellectual disability with marfanoid habitus;C3698541:Blepharophimosis - intellectual disability syndrome, MKB type;C5399762:FG syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg | Aug 01, 2017 | De novo missense variant identified in a female with severe ID, behavioral anomalies. Mutations in MED12 have been reported with different, syndromic X-linked recessive ID disorders . In the light of the recent identification of de novo mutations in initially X-linked recessive genes in severely affected females this variant might be pathogenic in a girl, but remains unclear at the moment. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at