13-108286850-A-G

Position:

• chr13-108286850-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006573.5(TNFSF13B):​c.472A>G​(p.Ile158Val) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TNFSF13B NM_006573.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40

Genes affected

TNFSF13B (HGNC:11929): (TNF superfamily member 13b) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for receptors TNFRSF13B/TACI, TNFRSF17/BCMA, and TNFRSF13C/BAFFR. This cytokine is expressed in B cell lineage cells, and acts as a potent B cell activator. It has been also shown to play an important role in the proliferation and differentiation of B cells. Alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Mar 2011]

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=0.1456334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF13B	NM_006573.5	c.472A>G	p.Ile158Val	missense_variant	3/6	ENST00000375887.9	NP_006564.1
TNFSF13B	XM_047430055.1	c.472A>G	p.Ile158Val	missense_variant	3/5		XP_047286011.1
TNFSF13B	NM_001145645.2	c.425-16403A>G		intron_variant			NP_001139117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF13B	ENST00000375887.9	c.472A>G	p.Ile158Val	missense_variant	3/6	1	NM_006573.5	ENSP00000365048	P1
TNFSF13B	ENST00000542136.1	c.472A>G	p.Ile158Val	missense_variant	3/4	1		ENSP00000445334
TNFSF13B	ENST00000430559.5	c.425-16403A>G		intron_variant		1		ENSP00000389540
TNFSF13B	ENST00000479435.1	n.246A>G		non_coding_transcript_exon_variant	2/5	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2022

The c.472A>G (p.I158V) alteration is located in exon 3 (coding exon 3) of the TNFSF13B gene. This alteration results from a A to G substitution at nucleotide position 472, causing the isoleucine (I) at amino acid position 158 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.60
DEOGEN2	Benign	0.23	T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	0.0046
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;M
MutationTaster	Benign	0.67	D;D;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.37	N;N
REVEL	Benign	0.050
Sift	Benign	0.20	T;T
Sift4G	Benign	0.66	T;T
Polyphen		0.0030	B;.
Vest4		0.29
MutPred		0.36		Gain of catalytic residue at Y163 (P = 0.0369);Gain of catalytic residue at Y163 (P = 0.0369);
MVP		0.30
MPC		0.40
ClinPred		0.49	T
GERP RS		5.2
Varity_R		0.20
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-108939198;