rs144410580
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_015335.5(MED13L):āc.1283A>Gā(p.His428Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00177 in 1,613,982 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0021 ( 4 hom., cov: 32)
Exomes š: 0.0017 ( 18 hom. )
Consequence
MED13L
NM_015335.5 missense, splice_region
NM_015335.5 missense, splice_region
Scores
1
8
9
Clinical Significance
Conservation
PhyloP100: 4.63
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 Benign. Variant got -15 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, MED13L
BP4
?
Computational evidence support a benign effect (MetaRNN=0.009149104).
BP6
?
Variant 12-116009130-T-C is Benign according to our data. Variant chr12-116009130-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 376878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-116009130-T-C is described in Lovd as [Likely_benign]. Variant chr12-116009130-T-C is described in Lovd as [Benign].
BS2
?
High Homozygotes in GnomAd4 at 4 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED13L | NM_015335.5 | c.1283A>G | p.His428Arg | missense_variant, splice_region_variant | 10/31 | ENST00000281928.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED13L | ENST00000281928.9 | c.1283A>G | p.His428Arg | missense_variant, splice_region_variant | 10/31 | 1 | NM_015335.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00207 AC: 315AN: 152154Hom.: 4 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00275 AC: 687AN: 250022Hom.: 6 AF XY: 0.00265 AC XY: 359AN XY: 135502
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GnomAD4 exome AF: 0.00174 AC: 2544AN: 1461710Hom.: 18 Cov.: 32 AF XY: 0.00173 AC XY: 1258AN XY: 727150
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GnomAD4 genome ? AF: 0.00207 AC: 315AN: 152272Hom.: 4 Cov.: 32 AF XY: 0.00274 AC XY: 204AN XY: 74458
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ESP6500AA
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ExAC
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | MED13L: BS1 - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Feb 03, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 11, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Transposition of the great arteries, dextro-looped Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;.
REVEL
Uncertain
Sift
Benign
D;.;.;.
Sift4G
Benign
T;.;.;.
Polyphen
D;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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