17-16940394-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012452.3(TNFRSF13B):​c.563A>G​(p.Lys188Arg) 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. 16/21 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)

Consequence

TNFRSF13B
NM_012452.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.140
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]

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ACMG classification

Classification made for transcript

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=0.08010912).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TNFRSF13BNM_012452.3 linkc.563A>G p.Lys188Arg missense_variant 4/5 ENST00000261652.7 NP_036584.1 O14836-1Q4ACX1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TNFRSF13BENST00000261652.7 linkc.563A>G p.Lys188Arg missense_variant 4/51 NM_012452.3 ENSP00000261652.2 O14836-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.025
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
5.8
DANN
Benign
0.60
DEOGEN2
Benign
0.11
T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.96
FATHMM_MKL
Benign
0.039
N
LIST_S2
Benign
0.63
T;T
M_CAP
Benign
0.061
D
MetaRNN
Benign
0.080
T;T
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
-1.4
N;.
PrimateAI
Benign
0.31
T
PROVEAN
Benign
1.1
N;.
REVEL
Benign
0.26
Sift
Benign
1.0
T;.
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;B
Vest4
0.15
MutPred
0.28
Loss of methylation at K188 (P = 0.0091);.;
MVP
0.61
MPC
0.012
ClinPred
0.036
T
GERP RS
2.4
Varity_R
0.025
gMVP
0.10

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.

Other links and lift over

dbSNP: rs74811083; hg19: chr17-16843708; API