Variant 13-108270079-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006573.5(TNFSF13B):c.184A>G(p.Thr62Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,114 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TNFSF13B
NM_006573.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06342384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TNFSF13B	NM_006573.5 linkuse as main transcript	c.184A>G	p.Thr62Ala	missense_variant	1/6	ENST00000375887.9	NP_006564.1
TNFSF13B	NM_001145645.2 linkuse as main transcript	c.184A>G	p.Thr62Ala	missense_variant	1/5		NP_001139117.1
TNFSF13B	XM_047430055.1 linkuse as main transcript	c.184A>G	p.Thr62Ala	missense_variant	1/5		XP_047286011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF13B	ENST00000375887.9 linkuse as main transcript	c.184A>G	p.Thr62Ala	missense_variant	1/6	1	NM_006573.5	ENSP00000365048	P1	Q9Y275-1
TNFSF13B	ENST00000430559.5 linkuse as main transcript	c.184A>G	p.Thr62Ala	missense_variant	1/5	1		ENSP00000389540		Q9Y275-2
TNFSF13B	ENST00000542136.1 linkuse as main transcript	c.184A>G	p.Thr62Ala	missense_variant	1/4	1		ENSP00000445334		Q9Y275-3
TNFSF13B	ENST00000486502.1 linkuse as main transcript	n.78-21A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000411

AC:

AN:

243022

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131998

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454114

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723690

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 09, 2024

The c.184A>G (p.T62A) alteration is located in exon 1 (coding exon 1) of the TNFSF13B gene. This alteration results from a A to G substitution at nucleotide position 184, causing the threonine (T) at amino acid position 62 to be replaced by an alanine (A). 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

0.072

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.45

DEOGEN2

Benign

0.16

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.48

T;T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.063

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.26

N;N;N

REVEL

Benign

0.074

Sift

Benign

0.75

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0050

B;B;.

Vest4

0.076

MutPred

0.55

Gain of catalytic residue at L61 (P = 8e-04);Gain of catalytic residue at L61 (P = 8e-04);Gain of catalytic residue at L61 (P = 8e-04);

MVP

0.22

MPC

0.47

ClinPred

0.049

GERP RS

-0.71

Varity_R

0.028

gMVP

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over