rs77400039
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_030973.4(MED25):c.165G>A(p.Thr55=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 1,614,030 control chromosomes in the GnomAD database, including 1,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.022 ( 83 hom., cov: 33)
Exomes 𝑓: 0.029 ( 1248 hom. )
Consequence
MED25
NM_030973.4 synonymous
NM_030973.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.285
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
Variant 19-49818601-G-A is Benign according to our data. Variant chr19-49818601-G-A is described in ClinVar as [Benign]. Clinvar id is 195384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49818601-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.285 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED25 | NM_030973.4 | c.165G>A | p.Thr55= | synonymous_variant | 2/18 | ENST00000312865.10 | |
MED25 | NM_001378355.1 | c.165G>A | p.Thr55= | synonymous_variant | 2/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED25 | ENST00000312865.10 | c.165G>A | p.Thr55= | synonymous_variant | 2/18 | 1 | NM_030973.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0223 AC: 3397AN: 152192Hom.: 80 Cov.: 33
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GnomAD3 exomes AF: 0.0355 AC: 8922AN: 251342Hom.: 362 AF XY: 0.0399 AC XY: 5424AN XY: 135876
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GnomAD4 exome AF: 0.0291 AC: 42509AN: 1461720Hom.: 1248 Cov.: 34 AF XY: 0.0318 AC XY: 23159AN XY: 727160
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GnomAD4 genome ? AF: 0.0224 AC: 3408AN: 152310Hom.: 83 Cov.: 33 AF XY: 0.0235 AC XY: 1753AN XY: 74474
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease Benign:1
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 | Eurofins Ntd Llc (ga) | Dec 02, 2014 | - - |
Charcot-Marie-Tooth disease type 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
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