chr22-42168711-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_001378418.1(TCF20):c.5825C>T(p.Pro1942Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,611,336 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. P1942A) 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 -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCF20 | NM_001378418.1 | c.5825C>T | p.Pro1942Leu | missense_variant | 5/6 | ENST00000677622.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCF20 | ENST00000677622.1 | c.5825C>T | p.Pro1942Leu | missense_variant | 5/6 | NM_001378418.1 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000288 AC: 7AN: 243466Hom.: 0 AF XY: 0.0000227 AC XY: 3AN XY: 131946
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1459076Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 725658
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152260Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74452
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 24, 2023 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 1918733). This variant has not been reported in the literature in individuals affected with TCF20-related conditions. This variant is present in population databases (rs144341537, gnomAD 0.02%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1942 of the TCF20 protein (p.Pro1942Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at