rs879253857
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_004608.4(TBX6):c.1179_1180delAG(p.Gly395LeufsTer91) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,436,914 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
TBX6
NM_004608.4 frameshift
NM_004608.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.709
Publications
5 publications found
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]
TBX6 Gene-Disease associations (from GenCC):
- Mayer-Rokitansky-Kuster-Hauser syndromeInheritance: AR Classification: STRONG Submitted by: PanelApp Australia
- spondylocostal dysostosis 5Inheritance: Unknown, AR, SD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
- autosomal dominant spondylocostal dysostosisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- congenital anomaly of kidney and urinary tractInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 8 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 16-30086355-CCT-C is Pathogenic according to our data. Variant chr16-30086355-CCT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 252362.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_004608.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TBX6 | TSL:1 MANE Select | c.1179_1180delAG | p.Gly395LeufsTer91 | frameshift | Exon 9 of 9 | ENSP00000378650.2 | O95947-1 | ||
| TBX6 | TSL:1 | c.1179_1180delAG | p.Gly395LeufsTer91 | frameshift | Exon 8 of 8 | ENSP00000279386.2 | O95947-1 | ||
| TBX6 | c.1275_1276delAG | p.Gly427LeufsTer91 | frameshift | Exon 8 of 8 | ENSP00000601643.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000139 AC: 2AN: 1436914Hom.: 0 AF XY: 0.00000140 AC XY: 1AN XY: 715122 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1436914
Hom.:
AF XY:
AC XY:
1
AN XY:
715122
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31608
American (AMR)
AF:
AC:
0
AN:
35550
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24800
East Asian (EAS)
AF:
AC:
0
AN:
39516
South Asian (SAS)
AF:
AC:
1
AN:
83058
European-Finnish (FIN)
AF:
AC:
0
AN:
53048
Middle Eastern (MID)
AF:
AC:
0
AN:
4944
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1105204
Other (OTH)
AF:
AC:
0
AN:
59186
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Spondylocostal dysostosis 5 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
Publications
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