chr6-131603129-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_004830.4(MED23):c.1832G>A(p.Arg611Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R611R) has been classified as Likely benign.
Frequency
Consequence
NM_004830.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152058Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251208Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135766
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461680Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 727150
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152058Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74268
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Published functional studies demonstrate a damaging effect; specifically, R617Q impairs the response of JUN and FOS immediate early genes to serum mitogens by altering the interaction between enhancer-bound transcription factors and Mediator (Hashimoto et al., 2011); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 21868677) -
Intellectual disability, autosomal recessive 18 Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at