19-1611727-T-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_003200.5(TCF3):āc.1945A>Cā(p.Asn649His) variant causes a missense change. The variant allele was found at a frequency of 0.0000266 in 1,613,570 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 (ā ā ).
Frequency
Consequence
NM_003200.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TCF3 | ENST00000262965.12 | c.1945A>C | p.Asn649His | missense_variant | Exon 19 of 19 | 1 | NM_003200.5 | ENSP00000262965.5 | ||
TCF3 | ENST00000588136.7 | c.1936A>C | p.Asn646His | missense_variant | Exon 19 of 20 | 2 | NM_001136139.4 | ENSP00000468487.1 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152020Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000440 AC: 11AN: 250268Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135544
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461432Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727006
GnomAD4 genome AF: 0.000164 AC: 25AN: 152138Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 12AN XY: 74382
ClinVar
Submissions by phenotype
TCF3-related disorder Uncertain:1
The TCF3 c.1945A>C variant is predicted to result in the amino acid substitution p.Asn649His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.060% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-1611726-T-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
not provided Uncertain:1
This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 649 of the TCF3 protein (p.Asn649His). This variant is present in population databases (rs372296344, gnomAD 0.06%). 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: 1045821). 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) has been performed 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. 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