chr16-30086239-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004608.4(TBX6):c.1297A>C(p.Lys433Gln) 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 1,611,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
TBX6
NM_004608.4 missense
NM_004608.4 missense
Scores
1
4
13
Clinical Significance
Conservation
PhyloP100: 2.00
Genes affected
TBX6 (HGNC:11605): (T-box transcription factor 6) This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. Knockout studies in mice indicate that this gene is important for specification of paraxial mesoderm structures. [provided by RefSeq, Aug 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.21332821).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX6 | NM_004608.4 | c.1297A>C | p.Lys433Gln | missense_variant | 9/9 | ENST00000395224.7 | |
TBX6 | XM_011545926.4 | c.1297A>C | p.Lys433Gln | missense_variant | 9/9 | ||
TBX6 | XM_047434551.1 | c.1297A>C | p.Lys433Gln | missense_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX6 | ENST00000395224.7 | c.1297A>C | p.Lys433Gln | missense_variant | 9/9 | 1 | NM_004608.4 | P1 | |
TBX6 | ENST00000279386.6 | c.1297A>C | p.Lys433Gln | missense_variant | 8/8 | 1 | P1 | ||
TBX6 | ENST00000567664.5 | c.*431A>C | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152062Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
8
AN:
152062
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 249160Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134886
GnomAD3 exomes
AF:
AC:
4
AN:
249160
Hom.:
AF XY:
AC XY:
2
AN XY:
134886
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1459522Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 726110
GnomAD4 exome
AF:
AC:
15
AN:
1459522
Hom.:
Cov.:
31
AF XY:
AC XY:
9
AN XY:
726110
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152062Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74298
GnomAD4 genome
?
AF:
AC:
8
AN:
152062
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
74298
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
2
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 1354234). This variant has not been reported in the literature in individuals affected with TBX6-related conditions. This variant is present in population databases (rs746202415, gnomAD 0.008%). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 433 of the TBX6 protein (p.Lys433Gln). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.
REVEL
Uncertain
Sift
Pathogenic
D;D;.
Sift4G
Benign
T;T;T
Polyphen
B;B;.
Vest4
MutPred
Loss of ubiquitination at K433 (P = 0.0063);Loss of ubiquitination at K433 (P = 0.0063);Loss of ubiquitination at K433 (P = 0.0063);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at