rs145574885
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 2P and 15B. PM2BP4_ModerateBP6_Very_StrongBP7BS1
The NM_030973.4(MED25):c.354C>T(p.Leu118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,614,128 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 1 hom. )
Consequence
MED25
NM_030973.4 synonymous
NM_030973.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.111
Genes affected
MED25 (HGNC:28845): (mediator complex subunit 25) This gene encodes a component of the transcriptional coactivator complex termed the Mediator complex. This complex is required for transcription of most RNA polymerase II-dependent genes. The encoded protein plays a role in chromatin modification and in preinitiation complex assembly. Mutations in this gene are associated with Charcot-Marie-Tooth disease type 2B2. [provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant 19-49828497-C-T is Benign according to our data. Variant chr19-49828497-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 329879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.111 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00108 (164/152326) while in subpopulation NFE AF= 0.00168 (114/68030). AF 95% confidence interval is 0.00143. There are 0 homozygotes in gnomad4. There are 83 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED25 | NM_030973.4 | c.354C>T | p.Leu118= | synonymous_variant | 4/18 | ENST00000312865.10 | |
MED25 | NM_001378355.1 | c.354C>T | p.Leu118= | synonymous_variant | 4/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED25 | ENST00000312865.10 | c.354C>T | p.Leu118= | synonymous_variant | 4/18 | 1 | NM_030973.4 | ||
MED25 | ENST00000595185.5 | c.354C>T | p.Leu118= | synonymous_variant | 4/7 | 1 | |||
MED25 | ENST00000538643.5 | c.181-2014C>T | intron_variant | 1 | |||||
MED25 | ENST00000593767.3 | c.354C>T | p.Leu118= | synonymous_variant | 4/18 | 3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00108 AC: 165AN: 152208Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00109 AC: 274AN: 251424Hom.: 0 AF XY: 0.00107 AC XY: 146AN XY: 135916
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GnomAD4 exome AF: 0.00136 AC: 1994AN: 1461802Hom.: 1 Cov.: 32 AF XY: 0.00134 AC XY: 978AN XY: 727200
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 11, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Charcot-Marie-Tooth disease type 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | MED25: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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