rs61754525
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_004268.5(MED17):āc.1449C>Gā(p.Gly483Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000682 in 1,611,988 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000046 ( 0 hom., cov: 32)
Exomes š: 0.000071 ( 0 hom. )
Consequence
MED17
NM_004268.5 synonymous
NM_004268.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.259
Genes affected
MED17 (HGNC:2375): (mediator complex subunit 17) The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 11-93801955-C-G is Benign according to our data. Variant chr11-93801955-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211480.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MED17 | NM_004268.5 | c.1449C>G | p.Gly483Gly | synonymous_variant | 9/12 | ENST00000251871.9 | NP_004259.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MED17 | ENST00000251871.9 | c.1449C>G | p.Gly483Gly | synonymous_variant | 9/12 | 1 | NM_004268.5 | ENSP00000251871.3 | ||
ENSG00000284057 | ENST00000638767.1 | c.2010C>G | p.Gly670Gly | synonymous_variant | 16/19 | 5 | ENSP00000492220.1 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 151992Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000879 AC: 22AN: 250402Hom.: 0 AF XY: 0.0000813 AC XY: 11AN XY: 135328
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GnomAD4 exome AF: 0.0000706 AC: 103AN: 1459878Hom.: 0 Cov.: 32 AF XY: 0.0000661 AC XY: 48AN XY: 726242
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74324
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 19, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 17, 2020 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 14, 2015 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 28, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 17
Find out detailed SpliceAI scores and Pangolin per-transcript scores at