chr16-30086268-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004608.4(TBX6):c.1268C>T(p.Ala423Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,612,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. A423A) has been classified as Likely benign.
Frequency
Consequence
NM_004608.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX6 | NM_004608.4 | c.1268C>T | p.Ala423Val | missense_variant | 9/9 | ENST00000395224.7 | |
TBX6 | XM_011545926.4 | c.1268C>T | p.Ala423Val | missense_variant | 9/9 | ||
TBX6 | XM_047434551.1 | c.1268C>T | p.Ala423Val | missense_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX6 | ENST00000395224.7 | c.1268C>T | p.Ala423Val | missense_variant | 9/9 | 1 | NM_004608.4 | P1 | |
TBX6 | ENST00000279386.6 | c.1268C>T | p.Ala423Val | missense_variant | 8/8 | 1 | P1 | ||
TBX6 | ENST00000567664.5 | c.*402C>T | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000724 AC: 18AN: 248628Hom.: 0 AF XY: 0.0000816 AC XY: 11AN XY: 134730
GnomAD4 exome AF: 0.000186 AC: 272AN: 1459960Hom.: 0 Cov.: 32 AF XY: 0.000198 AC XY: 144AN XY: 726304
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74346
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 05, 2023 | The c.1268C>T (p.A423V) alteration is located in exon 9 (coding exon 8) of the TBX6 gene. This alteration results from a C to T substitution at nucleotide position 1268, causing the alanine (A) at amino acid position 423 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 423 of the TBX6 protein (p.Ala423Val). This variant is present in population databases (rs201930048, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TBX6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1040034). 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