chr22-42168694-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_001378418.1(TCF20):c.5842G>A(p.Ala1948Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,610,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. A1948G) has been classified as Likely benign.
Frequency
Consequence
NM_001378418.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCF20 | NM_001378418.1 | c.5842G>A | p.Ala1948Thr | missense_variant | 5/6 | ENST00000677622.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCF20 | ENST00000677622.1 | c.5842G>A | p.Ala1948Thr | missense_variant | 5/6 | NM_001378418.1 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152028Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000657 AC: 16AN: 243696Hom.: 0 AF XY: 0.0000682 AC XY: 9AN XY: 131968
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1458492Hom.: 0 Cov.: 31 AF XY: 0.0000386 AC XY: 28AN XY: 725338
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152146Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74368
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1948 of the TCF20 protein (p.Ala1948Thr). This variant is present in population databases (rs539500058, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with TCF20-related conditions. ClinVar contains an entry for this variant (Variation ID: 1948741). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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