rs144457722
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6
The NM_015335.5(MED13L):c.1904G>A(p.Ser635Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000239 in 1,613,902 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 1 hom. )
Consequence
MED13L
NM_015335.5 missense
NM_015335.5 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 3.89
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 Likely_benign. Variant got -4 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, MED13L
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008439213).
BP6
?
Variant 12-116008509-C-T is Benign according to our data. Variant chr12-116008509-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 431731.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED13L | NM_015335.5 | c.1904G>A | p.Ser635Asn | missense_variant | 10/31 | ENST00000281928.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED13L | ENST00000281928.9 | c.1904G>A | p.Ser635Asn | missense_variant | 10/31 | 1 | NM_015335.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00130 AC: 198AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000331 AC: 83AN: 250872Hom.: 0 AF XY: 0.000229 AC XY: 31AN XY: 135598
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GnomAD4 exome AF: 0.000128 AC: 187AN: 1461598Hom.: 1 Cov.: 30 AF XY: 0.000100 AC XY: 73AN XY: 727096
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GnomAD4 genome ? AF: 0.00130 AC: 198AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.00115 AC XY: 86AN XY: 74468
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Cardiac anomalies - developmental delay - facial dysmorphism syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | research | TIDEX, University of British Columbia | - | - - |
MED13L-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 17, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 25, 2019 | This variant is associated with the following publications: (PMID: 30542205) - |
Transposition of the great arteries, dextro-looped Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 02, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.
REVEL
Benign
Sift
Benign
T;.;.
Sift4G
Benign
T;.;.
Polyphen
B;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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