rs748555967
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001083962.2(TCF4):c.851A>G(p.His284Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,118 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H284Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_001083962.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCF4 | NM_001083962.2 | c.851A>G | p.His284Arg | missense_variant | 11/20 | ENST00000354452.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCF4 | ENST00000354452.8 | c.851A>G | p.His284Arg | missense_variant | 11/20 | 5 | NM_001083962.2 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251030Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135678
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461118Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726864
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Pitt-Hopkins syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 24, 2016 | This sequence change replaces histidine with arginine at codon 284 of the TCF4 protein (p.His284Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is present in population databases (rs748555967, ExAC 0.003%) but has not been reported in the literature in individuals with a TCF4-related disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at