13-108270100-G-C

Variant names:

• chr13-108270100-G-C
• rs1303186225
• NM_006573.5:c.205G>C

Variant summary

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

The NM_006573.5(TNFSF13B):​c.205G>C​(p.Val69Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TNFSF13B NM_006573.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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=0.08238393).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF13B	NM_006573.5	c.205G>C	p.Val69Leu	missense_variant	Exon 1 of 6	ENST00000375887.9	NP_006564.1
TNFSF13B	NM_001145645.2	c.205G>C	p.Val69Leu	missense_variant	Exon 1 of 5		NP_001139117.1
TNFSF13B	XM_047430055.1	c.205G>C	p.Val69Leu	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.205G>C	p.Val69Leu	missense_variant	Exon 1 of 6	1	NM_006573.5	ENSP00000365048.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000830 AC: 2 AN: 241088 Hom.: 0 AF XY: 0.0000153 AC XY: 2 AN XY: 131048

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451626 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722486

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	17
DANN	Benign	0.59
DEOGEN2	Benign	0.17	.;T;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.61	T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.082	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.53	N;N;N
REVEL	Benign	0.030
Sift	Benign	0.40	T;T;T
Sift4G	Benign	0.54	T;T;T
Polyphen		0.0050	B;B;.
Vest4		0.11
MutPred		0.42		Gain of catalytic residue at G74 (P = 0.0011);Gain of catalytic residue at G74 (P = 0.0011);Gain of catalytic residue at G74 (P = 0.0011);
MVP		0.082
MPC		0.47
ClinPred		0.021	T
GERP RS		1.1
Varity_R		0.036
gMVP		0.25

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

LitVar

Other links and lift over

dbSNP: rs1303186225; hg19: chr13-108922448; COSMIC: COSV65516367; COSMIC: COSV65516367;