Genetic Variant TNFSF13:p.Asn96Ile (chr17-7559652-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003808.4(TNFSF13):c.287A>T(p.Asn96Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N96S) has been classified as Benign.

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TNFSF13
NM_003808.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14

Publications

123 publications found

Variant links:

Genes affected

TNFSF13 (HGNC:11928): (TNF superfamily member 13) The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF17/BCMA, a member of the TNF receptor family. This protein and its receptor are both found to be important for B cell development. In vitro experiments suggested that this protein may be able to induce apoptosis through its interaction with other TNF receptor family proteins such as TNFRSF6/FAS and TNFRSF14/HVEM. Alternative splicing results in multiple transcript variants. Some transcripts that skip the last exon of the upstream gene (TNFSF12) and continue into the second exon of this gene have been identified; such read-through transcripts are contained in GeneID 407977, TNFSF12-TNFSF13. [provided by RefSeq, Oct 2010]

TNFSF13 links:

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]

TNFSF12-TNFSF13 links:

ENSG00000276384 (HGNC:):

ENSG00000276384 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22158253).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003808.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TNFSF13	NM_003808.4	MANE Select	c.287A>T	p.Asn96Ile	missense	Exon 2 of 6	NP_003799.1
TNFSF12-TNFSF13	NM_172089.4		c.527A>T	p.Asn176Ile	missense	Exon 7 of 11	NP_742086.1
TNFSF13	NM_172088.4		c.287A>T	p.Asn96Ile	missense	Exon 2 of 7	NP_742085.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TNFSF13	ENST00000338784.9	TSL:1 MANE Select	c.287A>T	p.Asn96Ile	missense	Exon 2 of 6	ENSP00000343505.4
TNFSF12-TNFSF13	ENST00000293826.4	TSL:1	c.527A>T	p.Asn176Ile	missense	Exon 7 of 11	ENSP00000293826.4
TNFSF13	ENST00000396545.4	TSL:1	c.287A>T	p.Asn96Ile	missense	Exon 2 of 7	ENSP00000379794.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1461288

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726892

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53180

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111794

Other (OTH)

AF:

0.00

AC:

AN:

60376

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.093

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

Eigen

Benign

-0.046

Eigen_PC

Benign

-0.018

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.22

MetaSVM

Uncertain

0.55

MutationAssessor

Benign

1.5

PhyloP100

1.1

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

REVEL

Benign

0.25

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.013

Polyphen

0.76

Vest4

0.38

MutPred

0.21

Loss of helix (P = 0.0558)

MVP

0.72

MPC

1.4

ClinPred

0.66

GERP RS

2.4

Varity_R

0.10

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over