X-71141247-A-ACAGCAG
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3BP6BS2
The NM_005120.3(MED12):c.6303_6308dup(p.Gln2114_Gln2115dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 110,133 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. Q2095Q) has been classified as Likely benign.
Frequency
Consequence
NM_005120.3 inframe_insertion
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.6303_6308dup | p.Gln2114_Gln2115dup | inframe_insertion | 43/45 | ENST00000374080.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED12 | ENST00000374080.8 | c.6303_6308dup | p.Gln2114_Gln2115dup | inframe_insertion | 43/45 | 1 | NM_005120.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000136 AC: 15AN: 110085Hom.: 0 Cov.: 23 AF XY: 0.000153 AC XY: 5AN XY: 32697
GnomAD3 exomes AF: 0.0000905 AC: 10AN: 110447Hom.: 0 AF XY: 0.0000516 AC XY: 2AN XY: 38777
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000467 AC: 49AN: 1049286Hom.: 0 Cov.: 32 AF XY: 0.0000440 AC XY: 15AN XY: 340908
GnomAD4 genome AF: 0.000136 AC: 15AN: 110133Hom.: 0 Cov.: 23 AF XY: 0.000153 AC XY: 5AN XY: 32753
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 05, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 15, 2016 | - - |
FG syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 21, 2023 | This variant, c.6303_6308dup, results in the insertion of 2 amino acid(s) of the MED12 protein (p.Gln2114_Gln2115dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MED12-related conditions. ClinVar contains an entry for this variant (Variation ID: 197488). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 27, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at