rs538831129
chr9-99105255-T-TGGCGGCGGCGGCchr9-99105255-T-TGGCGGCGGCGGCGGCGGCchr9-99105255-T-TGGCGGCchr9-99105255-T-TGGCchr9-99105255-TGGCGGCGGCGGCGGC-Tchr9-99105255-TGGC-Tchr9-99105255-T-TGGCGGCGGCchr9-99105255-TGGCGGCGGCGGCGGCGGC-Tchr9-99105255-TGGCGGCGGCGGC-Tchr9-99105255-TGGCGGC-Tchr9-99105255-T-TGGCGGCGGCGGCGGCchr9-99105255-TGGCGGCGGC-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_004612.4(TGFBR1):c.67_78dup(p.Ala23_Ala26dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. L17L) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000033 ( 0 hom. )
Consequence
TGFBR1
NM_004612.4 inframe_insertion
NM_004612.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.987
Genes affected
TGFBR1 (HGNC:11772): (transforming growth factor beta receptor 1) The protein encoded by this gene forms a heteromeric complex with type II TGF-beta receptors when bound to TGF-beta, transducing the TGF-beta signal from the cell surface to the cytoplasm. The encoded protein is a serine/threonine protein kinase. Mutations in this gene have been associated with Loeys-Dietz aortic aneurysm syndrome (LDAS). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFBR1 | NM_004612.4 | c.67_78dup | p.Ala23_Ala26dup | inframe_insertion | 1/9 | ENST00000374994.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFBR1 | ENST00000374994.9 | c.67_78dup | p.Ala23_Ala26dup | inframe_insertion | 1/9 | 1 | NM_004612.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD3 genomes
?
Cov.:
30
GnomAD4 exome AF: 0.00000333 AC: 3AN: 900968Hom.: 0 Cov.: 7 AF XY: 0.00000473 AC XY: 2AN XY: 422762
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GnomAD4 genome ? Cov.: 30
GnomAD4 genome
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Cov.:
30
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Multiple self-healing squamous epithelioma;C4551955:Loeys-Dietz syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 22, 2021 | - - |
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 30, 2020 | This variant, c.67_78dup, results in the insertion of 4 amino acid(s) to the TGFBR1 protein (p.Ala23_Ala26dup), but otherwise preserves the integrity of the reading frame. 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with TGFBR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 543893). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at