16-30086325-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004608.4(TBX6):c.1211C>T(p.Ala404Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,606,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A404A) has been classified as Likely benign.
Frequency
Consequence
NM_004608.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX6 | NM_004608.4 | c.1211C>T | p.Ala404Val | missense_variant | 9/9 | ENST00000395224.7 | |
TBX6 | XM_011545926.4 | c.1211C>T | p.Ala404Val | missense_variant | 9/9 | ||
TBX6 | XM_047434551.1 | c.1211C>T | p.Ala404Val | missense_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX6 | ENST00000395224.7 | c.1211C>T | p.Ala404Val | missense_variant | 9/9 | 1 | NM_004608.4 | P1 | |
TBX6 | ENST00000279386.6 | c.1211C>T | p.Ala404Val | missense_variant | 8/8 | 1 | P1 | ||
TBX6 | ENST00000567664.5 | c.*345C>T | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000464 AC: 11AN: 237046Hom.: 0 AF XY: 0.0000307 AC XY: 4AN XY: 130106
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1454158Hom.: 0 Cov.: 34 AF XY: 0.0000138 AC XY: 10AN XY: 723668
GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74326
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with TBX6-related conditions. This variant is present in population databases (rs142143210, gnomAD 0.03%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 404 of the TBX6 protein (p.Ala404Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at