NM_003809.3:c.597G>T
Variant names:
Variant summary
Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_003809.3(TNFSF12):c.597G>T(p.Ala199Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,459,810 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A199A) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
TNFSF12
NM_003809.3 synonymous
NM_003809.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.26
Publications
0 publications found
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]
TNFSF12-TNFSF13 (HGNC:33537): (TNFSF12-TNFSF13 readthrough) This gene encodes a member of the tumor necrosis factor superfamily. It encodes a hybrid protein composed of the cytoplasmic and transmembrane domains of family member 12 fused to the C-terminal domain of family member 13. The hybrid protein is membrane anchored and presents the receptor-binding domain of family member 13 at the cell surface. It stimulates cycling in T- and B-lymphoma cell lines. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 17-7557197-G-T is Benign according to our data. Variant chr17-7557197-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3622478.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.26 with no splicing effect.
BS2
High AC in GnomAdExome4 at 20 AD gene.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_003809.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TNFSF12 | NM_003809.3 | MANE Select | c.597G>T | p.Ala199Ala | synonymous | Exon 7 of 7 | NP_003800.1 | ||
| TNFSF12 | NR_037146.2 | n.932G>T | non_coding_transcript_exon | Exon 8 of 8 | |||||
| TNFSF12-TNFSF13 | NM_172089.4 | c.498+295G>T | intron | N/A | NP_742086.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TNFSF12 | ENST00000293825.11 | TSL:1 MANE Select | c.597G>T | p.Ala199Ala | synonymous | Exon 7 of 7 | ENSP00000293825.6 | ||
| TNFSF12 | ENST00000322272.11 | TSL:1 | n.*431G>T | non_coding_transcript_exon | Exon 8 of 8 | ENSP00000314636.7 | |||
| TNFSF12 | ENST00000322272.11 | TSL:1 | n.*431G>T | 3_prime_UTR | Exon 8 of 8 | ENSP00000314636.7 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD2 exomes AF: 0.00 AC: 0AN: 250888 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
250888
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1459810Hom.: 0 Cov.: 49 AF XY: 0.00000964 AC XY: 7AN XY: 726276 show subpopulations
GnomAD4 exome
AF:
AC:
20
AN:
1459810
Hom.:
Cov.:
49
AF XY:
AC XY:
7
AN XY:
726276
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33440
American (AMR)
AF:
AC:
1
AN:
44652
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26098
East Asian (EAS)
AF:
AC:
0
AN:
39690
South Asian (SAS)
AF:
AC:
0
AN:
86186
European-Finnish (FIN)
AF:
AC:
0
AN:
53062
Middle Eastern (MID)
AF:
AC:
1
AN:
5758
European-Non Finnish (NFE)
AF:
AC:
18
AN:
1110594
Other (OTH)
AF:
AC:
0
AN:
60330
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
31
Alfa
AF:
Hom.:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Common variable immunodeficiency Benign:1
May 25, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
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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