NM_005996.4:c.254C>T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_005996.4(TBX3):c.254C>T(p.Ala85Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A85E) has been classified as Uncertain significance.
Frequency
Consequence
NM_005996.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TBX3 | NM_005996.4 | c.254C>T | p.Ala85Val | missense_variant | Exon 1 of 7 | ENST00000349155.7 | NP_005987.3 | |
TBX3 | NM_016569.4 | c.254C>T | p.Ala85Val | missense_variant | Exon 1 of 8 | NP_057653.3 | ||
TBX3-AS1 | NR_187552.1 | n.343+313G>A | intron_variant | Intron 1 of 1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250304Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135714
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727244
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
TBX3-related disorder Uncertain:1
The TBX3 c.254C>T variant is predicted to result in the amino acid substitution p.Ala85Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at