rs80338915
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_003221.4(TFAP2B):c.854G>A(p.Arg285Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 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 (★★).
Frequency
Consequence
NM_003221.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727246
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Char syndrome Pathogenic:2Other:1
This variant was identified in an Australian family of Caucasian descent. This novel missense mutation (with respect to ExAC) segregates completely with disease in 7 individuals across 3 generations. All carriers of this variant exhibit suble characteristic CHAR syndrome features, except one individual who appears asymptomatic, suggesting incomplete penetrance of this variant. -
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not provided Pathogenic:1
Published functional studies suggest a damaging effect; specifically, expression studies indicate R274Q results in reduced transactivation function via decreased DNA binding capacity (Zhao et al., 2001); Not observed in large population cohorts (gnomAD); Known as R274Q by alternate nomenclature; This variant is associated with the following publications: (PMID: 29555671, 11505339, 25500235) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at