chr19-1611718-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003200.5(TCF3):c.1954G>A(p.Gly652Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G652G) has been classified as Likely benign.
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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCF3 | NM_003200.5 | c.1954G>A | p.Gly652Arg | missense_variant | 19/19 | ENST00000262965.12 | |
TCF3 | NM_001136139.4 | c.1945G>A | p.Gly649Arg | missense_variant | 19/20 | ENST00000588136.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCF3 | ENST00000262965.12 | c.1954G>A | p.Gly652Arg | missense_variant | 19/19 | 1 | NM_003200.5 | A1 | |
TCF3 | ENST00000588136.7 | c.1945G>A | p.Gly649Arg | missense_variant | 19/20 | 2 | NM_001136139.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152078Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249754Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135294
GnomAD4 exome AF: 0.00000890 AC: 13AN: 1460962Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 726732
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152078Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74290
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2022 | 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TCF3 protein function. ClinVar contains an entry for this variant (Variation ID: 1465289). This variant has not been reported in the literature in individuals affected with TCF3-related conditions. This variant is present in population databases (rs755856969, gnomAD 0.004%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 652 of the TCF3 protein (p.Gly652Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at