17-7549228-G-GCTGGGC
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP3
The NM_003809.3(TNFSF12):c.86_91dup(p.Gly29_Leu30dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,215,770 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
TNFSF12
NM_003809.3 inframe_insertion
NM_003809.3 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.03
Genes affected
TNFSF12 (HGNC:11927): (TNF superfamily member 12) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is a ligand for the FN14/TWEAKR receptor. This cytokine has overlapping signaling functions with TNF, but displays a much wider tissue distribution. This cytokine, which exists in both membrane-bound and secreted forms, can induce apoptosis via multiple pathways of cell death in a cell type-specific manner. This cytokine is also found to promote proliferation and migration of endothelial cells, and thus acts as a regulator of angiogenesis. Alternative splicing results in multiple transcript variants. Some transcripts skip the last exon of this gene and continue into the second exon of the neighboring TNFSF13 gene; such read-through transcripts are contained in GeneID 407977, TNFSF12-TNFSF13. [provided by RefSeq, Oct 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_003809.3
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNFSF12 | NM_003809.3 | c.86_91dup | p.Gly29_Leu30dup | inframe_insertion | 1/7 | ENST00000293825.11 | |
TNFSF12-TNFSF13 | NM_172089.4 | c.86_91dup | p.Gly29_Leu30dup | inframe_insertion | 1/11 | ||
TNFSF12 | NR_037146.2 | n.182_187dup | non_coding_transcript_exon_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNFSF12 | ENST00000293825.11 | c.86_91dup | p.Gly29_Leu30dup | inframe_insertion | 1/7 | 1 | NM_003809.3 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000411 AC: 5AN: 1215770Hom.: 0 Cov.: 32 AF XY: 0.00000338 AC XY: 2AN XY: 591692
GnomAD4 exome
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32
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2
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591692
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Common variable immunodeficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 07, 2022 | 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 affected with TNFSF12-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.86_91dup, results in the insertion of 2 amino acid(s) of the TNFSF12 protein (p.Gly29_Leu30dup), but otherwise preserves the integrity of the reading frame. - |
Computational scores
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Calibrated prediction
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.