GeneBe

rs55916807

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012452.3(TNFRSF13B):​c.215G>T​(p.Arg72Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R72C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

TNFRSF13B
NM_012452.3 missense

Scores

6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.12

Publications

0 publications found
Variant links:
Genes affected
TNFRSF13B (HGNC:18153): (TNF receptor superfamily member 13B) The protein encoded by this gene is a lymphocyte-specific member of the tumor necrosis factor (TNF) receptor superfamily. It interacts with calcium-modulator and cyclophilin ligand (CAML). The protein induces activation of the transcription factors NFAT, AP1, and NF-kappa-B and plays a crucial role in humoral immunity by interacting with a TNF ligand. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]
TNFRSF13B Gene-Disease associations (from GenCC):
  • immunodeficiency, common variable, 2
    Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen, G2P, Ambry Genetics
  • common variable immunodeficiency
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012452.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TNFRSF13B
NM_012452.3
MANE Select
c.215G>Tp.Arg72Leu
missense
Exon 3 of 5NP_036584.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TNFRSF13B
ENST00000261652.7
TSL:1 MANE Select
c.215G>Tp.Arg72Leu
missense
Exon 3 of 5ENSP00000261652.2
TNFRSF13B
ENST00000583789.1
TSL:1
c.77G>Tp.Arg26Leu
missense
Exon 2 of 4ENSP00000462952.1
TNFRSF13B
ENST00000579315.5
TSL:3
c.215G>Tp.Arg72Leu
missense
Exon 3 of 4ENSP00000464069.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
32

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
Immunodeficiency, common variable, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Uncertain
0.033
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
8.1
DANN
Benign
0.47
DEOGEN2
Uncertain
0.60
D
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.070
N
LIST_S2
Benign
0.67
T
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.46
T
MetaSVM
Uncertain
-0.23
T
MutationAssessor
Benign
0.36
N
PhyloP100
-1.1
PrimateAI
Benign
0.27
T
PROVEAN
Uncertain
-3.2
D
REVEL
Uncertain
0.30
Sift
Benign
0.12
T
Sift4G
Benign
0.10
T
Polyphen
0.0030
B
Vest4
0.26
MutPred
0.91
Gain of ubiquitination at K73 (P = 0.0462)
MVP
0.25
MPC
0.015
ClinPred
0.053
T
GERP RS
-9.9
Varity_R
0.21
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs55916807; hg19: chr17-16852282; API