13-108270038-T-A

Position:

• chr13-108270038-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006573.5(TNFSF13B):​c.143T>A​(p.Leu48Gln) 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 pathogenic outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNFSF13B NM_006573.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03

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]

TNFSF13B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF13B	NM_006573.5	c.143T>A	p.Leu48Gln	missense_variant	1/6	ENST00000375887.9	NP_006564.1
TNFSF13B	NM_001145645.2	c.143T>A	p.Leu48Gln	missense_variant	1/5		NP_001139117.1
TNFSF13B	XM_047430055.1	c.143T>A	p.Leu48Gln	missense_variant	1/5		XP_047286011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF13B	ENST00000375887.9	c.143T>A	p.Leu48Gln	missense_variant	1/6	1	NM_006573.5	ENSP00000365048.3
TNFSF13B	ENST00000430559.5	c.143T>A	p.Leu48Gln	missense_variant	1/5	1		ENSP00000389540.1
TNFSF13B	ENST00000542136.1	c.143T>A	p.Leu48Gln	missense_variant	1/4	1		ENSP00000445334.1
TNFSF13B	ENST00000486502.1	n.78-62T>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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 08, 2021

The c.143T>A (p.L48Q) alteration is located in exon 1 (coding exon 1) of the TNFSF13B gene. This alteration results from a T to A substitution at nucleotide position 143, causing the leucine (L) at amino acid position 48 to be replaced by a glutamine (Q). 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	0.14
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	.;T;.
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.85	T;T;T
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	2.0	M;M;M
MutationTaster	Benign	0.75	N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.8	N;N;D
REVEL	Benign	0.29
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.045	D;T;D
Polyphen		1.0	D;D;.
Vest4		0.76
MutPred		0.47		Gain of disorder (P = 0.042);Gain of disorder (P = 0.042);Gain of disorder (P = 0.042);
MVP		0.47
MPC		1.4
ClinPred		0.73	D
GERP RS		3.5
Varity_R		0.19
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr13-108922386;