chr9-27157916-C-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000459.5(TEK):c.138C>T(p.Ala46=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,614,062 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0071 ( 12 hom., cov: 32)
Exomes 𝑓: 0.00068 ( 13 hom. )
Consequence
TEK
NM_000459.5 synonymous
NM_000459.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.14
Genes affected
TEK (HGNC:11724): (TEK receptor tyrosine kinase) This gene encodes a receptor that belongs to the protein tyrosine kinase Tie2 family. The encoded protein possesses a unique extracellular region that contains two immunoglobulin-like domains, three epidermal growth factor (EGF)-like domains and three fibronectin type III repeats. The ligand angiopoietin-1 binds to this receptor and mediates a signaling pathway that functions in embryonic vascular development. Mutations in this gene are associated with inherited venous malformations of the skin and mucous membranes. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 9-27157916-C-T is Benign according to our data. Variant chr9-27157916-C-T is described in ClinVar as [Benign]. Clinvar id is 366391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.14 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00714 (1086/152178) while in subpopulation AFR AF= 0.025 (1038/41516). AF 95% confidence interval is 0.0237. There are 12 homozygotes in gnomad4. There are 522 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1086 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TEK | NM_000459.5 | c.138C>T | p.Ala46= | synonymous_variant | 2/23 | ENST00000380036.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TEK | ENST00000380036.10 | c.138C>T | p.Ala46= | synonymous_variant | 2/23 | 1 | NM_000459.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00712 AC: 1083AN: 152060Hom.: 12 Cov.: 32
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GnomAD3 exomes AF: 0.00182 AC: 457AN: 251360Hom.: 6 AF XY: 0.00135 AC XY: 184AN XY: 135846
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GnomAD4 exome AF: 0.000677 AC: 990AN: 1461884Hom.: 13 Cov.: 31 AF XY: 0.000579 AC XY: 421AN XY: 727244
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GnomAD4 genome AF: 0.00714 AC: 1086AN: 152178Hom.: 12 Cov.: 32 AF XY: 0.00702 AC XY: 522AN XY: 74400
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 17, 2021 | - - |
Multiple cutaneous and mucosal venous malformations Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at