17-7559652-A-T

Position:

• chr17-7559652-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 12/21 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 Likely benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNFSF13 NM_003808.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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]

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]

TNFSF13 (HGNC:):

ACMG classification

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=0.22158253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF13	NM_003808.4	c.287A>T	p.Asn96Ile	missense_variant	2/6	ENST00000338784.9	NP_003799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF13	ENST00000338784.9	c.287A>T	p.Asn96Ile	missense_variant	2/6	1	NM_003808.4	ENSP00000343505.4
TNFSF12-TNFSF13	ENST00000293826.4	c.527A>T	p.Asn176Ile	missense_variant	7/11	1		ENSP00000293826.4

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1461288 Hom.: 0 Cov.: 82 AF XY: 0.00 AC XY: 0 AN XY: 726892

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	.;T;.;.;T;.
Eigen	Benign	-0.046
Eigen_PC	Benign	-0.018
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;D
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.22	T;T;T;T;T;T
MetaSVM	Uncertain	0.55	D
MutationAssessor	Benign	1.5	.;.;.;L;L;L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N;N;N;N;N;N
REVEL	Benign	0.25
Sift	Uncertain	0.0050	D;D;D;D;D;D
Sift4G	Uncertain	0.013	D;D;D;T;T;T
Polyphen		0.76, 0.11, 0.43	.;.;.;P;B;B
Vest4		0.38
MutPred		0.21		.;.;.;Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.72
MPC		1.4
ClinPred		0.66	D
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

LitVar

Other links and lift over

dbSNP: rs3803800; hg19: chr17-7462969;