chr9-114790814-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005118.4(TNFSF15):c.394A>G(p.Met132Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,968 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 0.00014 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
TNFSF15
NM_005118.4 missense
NM_005118.4 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 3.24
Genes affected
TNFSF15 (HGNC:11931): (TNF superfamily member 15) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is abundantly expressed in endothelial cells, but is not expressed in either B or T cells. The expression of this protein is inducible by TNF and IL-1 alpha. This cytokine is a ligand for receptor TNFRSF25 and decoy receptor TNFRSF21/DR6. It can activate NF-kappaB and MAP kinases, and acts as an autocrine factor to induce apoptosis in endothelial cells. This cytokine is also found to inhibit endothelial cell proliferation, and thus may function as an angiogenesis inhibitor. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]
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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=0.25465685).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNFSF15 | NM_005118.4 | c.394A>G | p.Met132Val | missense_variant | 4/4 | ENST00000374045.5 | |
TNFSF15 | NM_001204344.1 | c.217A>G | p.Met73Val | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNFSF15 | ENST00000374045.5 | c.394A>G | p.Met132Val | missense_variant | 4/4 | 1 | NM_005118.4 | P1 | |
TNFSF15 | ENST00000374044.1 | c.163A>G | p.Met55Val | missense_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152084Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251148Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135740
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461884Hom.: 0 Cov.: 36 AF XY: 0.00000550 AC XY: 4AN XY: 727242
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GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152084Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 16AN XY: 74284
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2022 | The c.394A>G (p.M132V) alteration is located in exon 4 (coding exon 4) of the TNFSF15 gene. This alteration results from a A to G substitution at nucleotide position 394, causing the methionine (M) at amino acid position 132 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Loss of methylation at K137 (P = 0.1136);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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