rs777818556
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_005120.3(MED12):c.6526C>T(p.Arg2176Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000662 in 1,208,997 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2176H) has been classified as Likely benign.
Frequency
Consequence
NM_005120.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED12 | NM_005120.3 | c.6526C>T | p.Arg2176Cys | missense_variant | 45/45 | ENST00000374080.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED12 | ENST00000374080.8 | c.6526C>T | p.Arg2176Cys | missense_variant | 45/45 | 1 | NM_005120.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000179 AC: 2AN: 111998Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34158
GnomAD3 exomes AF: 0.00000551 AC: 1AN: 181478Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67436
GnomAD4 exome AF: 0.00000547 AC: 6AN: 1096999Hom.: 0 Cov.: 30 AF XY: 0.00000828 AC XY: 3AN XY: 362465
GnomAD4 genome AF: 0.0000179 AC: 2AN: 111998Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34158
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 25, 2020 | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016), including in the hemizygous state in one individual; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID# 426569; Landrum et al., 2016) - |
FG syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at