19-1611714-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_003200.5(TCF3):āc.1958A>Cā(p.His653Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,612,808 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 Uncertain significance (ā ).
Frequency
Consequence
NM_003200.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TCF3 | ENST00000262965.12 | c.1958A>C | p.His653Pro | missense_variant | Exon 19 of 19 | 1 | NM_003200.5 | ENSP00000262965.5 | ||
TCF3 | ENST00000588136.7 | c.1949A>C | p.His650Pro | missense_variant | Exon 19 of 20 | 2 | NM_001136139.4 | ENSP00000468487.1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152000Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249634Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135230
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460808Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726676
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152000Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74232
ClinVar
Submissions by phenotype
not provided Uncertain:1
Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TCF3 protein function. This variant has not been reported in the literature in individuals affected with TCF3-related conditions. This variant is present in population databases (rs368510078, gnomAD 0.007%). This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 653 of the TCF3 protein (p.His653Pro). 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