13-108270047-C-G

Variant names:

• chr13-108270047-C-G
• NM_006573.5:c.152C>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.152C>G​(p.Thr51Ser) 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: 32)
• Consequence: TNFSF13B NM_006573.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.87

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=0.19325957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF13B	NM_006573.5	c.152C>G	p.Thr51Ser	missense_variant	Exon 1 of 6	ENST00000375887.9	NP_006564.1
TNFSF13B	NM_001145645.2	c.152C>G	p.Thr51Ser	missense_variant	Exon 1 of 5		NP_001139117.1
TNFSF13B	XM_047430055.1	c.152C>G	p.Thr51Ser	missense_variant	Exon 1 of 5		XP_047286011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF13B	ENST00000375887.9	c.152C>G	p.Thr51Ser	missense_variant	Exon 1 of 6	1	NM_006573.5	ENSP00000365048.3

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

Feb 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.152C>G (p.T51S) alteration is located in exon 1 (coding exon 1) of the TNFSF13B gene. This alteration results from a C to G substitution at nucleotide position 152, causing the threonine (T) at amino acid position 51 to be replaced by a serine (S). 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	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.41	.;T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.51	T;T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.3	N;N;D
REVEL	Benign	0.12
Sift	Uncertain	0.014	D;D;T
Sift4G	Benign	0.10	T;T;D
Polyphen		0.67	P;P;.
Vest4		0.26
MutPred		0.38		Gain of catalytic residue at T51 (P = 0.0041);Gain of catalytic residue at T51 (P = 0.0041);Gain of catalytic residue at T51 (P = 0.0041);
MVP		0.39
MPC		0.44
ClinPred		0.55	D
GERP RS		4.2
Varity_R		0.048
gMVP		0.34

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: chr13-108922395;