rs7252811
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003200.5(TCF3):c.1948C>T(p.Pro650Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,504 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003200.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TCF3 | ENST00000262965.12 | c.1948C>T | p.Pro650Ser | missense_variant | Exon 19 of 19 | 1 | NM_003200.5 | ENSP00000262965.5 | ||
TCF3 | ENST00000588136.7 | c.1939C>T | p.Pro647Ser | missense_variant | Exon 19 of 20 | 2 | NM_001136139.4 | ENSP00000468487.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152120Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250136Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135464
GnomAD4 exome AF: 0.0000541 AC: 79AN: 1461384Hom.: 0 Cov.: 31 AF XY: 0.0000509 AC XY: 37AN XY: 726982
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152120Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74310
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 650 of the TCF3 protein (p.Pro650Ser). This variant is present in population databases (rs7252811, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TCF3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1518917). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TCF3 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at