rs1555246952
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_015335.5(MED13L):c.2504del(p.Pro835LeufsTer46) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
MED13L
NM_015335.5 frameshift
NM_015335.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.81
Genes affected
MED13L (HGNC:22962): (mediator complex subunit 13L) The protein encoded by this gene is a subunit of the Mediator complex, a large complex of proteins that functions as a transcriptional coactivator for most RNA polymerase II-transcribed genes. The encoded protein is involved in early development of the heart and brain. Defects in this gene are a cause of transposition of the great arteries, dextro-looped (DTGA).[provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 12-116003067-AG-A is Pathogenic according to our data. Variant chr12-116003067-AG-A is described in ClinVar as [Pathogenic]. Clinvar id is 427896.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED13L | NM_015335.5 | c.2504del | p.Pro835LeufsTer46 | frameshift_variant | 14/31 | ENST00000281928.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED13L | ENST00000281928.9 | c.2504del | p.Pro835LeufsTer46 | frameshift_variant | 14/31 | 1 | NM_015335.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cardiac anomalies - developmental delay - facial dysmorphism syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Medical Genetics, University of Zurich | May 18, 2017 | - - |
Computational scores
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Calibrated prediction
Score
Prediction
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at