19-49818377-G-C
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_030973.4(MED25):āc.36G>Cā(p.Gly12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
MED25
NM_030973.4 synonymous
NM_030973.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.16
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 Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant 19-49818377-G-C is Benign according to our data. Variant chr19-49818377-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1950167.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.16 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MED25 | NM_030973.4 | c.36G>C | p.Gly12= | synonymous_variant | 1/18 | ENST00000312865.10 | NP_112235.2 | |
MED25 | NM_001378355.1 | c.36G>C | p.Gly12= | synonymous_variant | 1/18 | NP_001365284.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MED25 | ENST00000312865.10 | c.36G>C | p.Gly12= | synonymous_variant | 1/18 | 1 | NM_030973.4 | ENSP00000326767 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000826 AC: 2AN: 242044Hom.: 0 AF XY: 0.0000152 AC XY: 2AN XY: 131834
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1459276Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3AN XY: 725828
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GnomAD4 genome Cov.: 33
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 04, 2022 | - - |
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