13-108270038-T-A

Variant names:

• chr13-108270038-T-A
• NM_006573.5:c.143T>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006573.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF13B	NM_006573.5	MANE Select	c.143T>A	p.Leu48Gln	missense	Exon 1 of 6	NP_006564.1	Q9Y275-1
	TNFSF13B	NM_001145645.2		c.143T>A	p.Leu48Gln	missense	Exon 1 of 5	NP_001139117.1	Q9Y275-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF13B	ENST00000375887.9	TSL:1 MANE Select	c.143T>A	p.Leu48Gln	missense	Exon 1 of 6	ENSP00000365048.3	Q9Y275-1
	TNFSF13B	ENST00000430559.5	TSL:1	c.143T>A	p.Leu48Gln	missense	Exon 1 of 5	ENSP00000389540.1	Q9Y275-2
	TNFSF13B	ENST00000542136.1	TSL:1	c.143T>A	p.Leu48Gln	missense	Exon 1 of 4	ENSP00000445334.1	Q9Y275-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.0
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.29
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.045	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.47		Gain of disorder (P = 0.042)
MVP		0.47
MPC		1.4
ClinPred		0.73	D
GERP RS		3.5
PromoterAI		-0.069	Neutral
Varity_R		0.19
gMVP		0.33
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

hg19: chr13-108922386;