7-35202453-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001077653.2(TBX20):c.1321G>C(p.Ala441Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,442,102 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A441V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001077653.2 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 |
---|---|---|---|---|---|---|---|
TBX20 | NM_001077653.2 | c.1321G>C | p.Ala441Pro | missense_variant | 8/8 | ENST00000408931.4 | |
TBX20 | XM_017012456.2 | c.724G>C | p.Ala242Pro | missense_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX20 | ENST00000408931.4 | c.1321G>C | p.Ala441Pro | missense_variant | 8/8 | 1 | NM_001077653.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.00000430 AC: 1AN: 232454Hom.: 0 AF XY: 0.00000796 AC XY: 1AN XY: 125588
GnomAD4 exome AF: 6.93e-7 AC: 1AN: 1442102Hom.: 0 Cov.: 33 AF XY: 0.00000140 AC XY: 1AN XY: 716072
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 19, 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. This variant has not been reported in the literature in individuals affected with TBX20-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 441 of the TBX20 protein (p.Ala441Pro). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at