rs11078355

chr17-16939598-A-Cchr17-16939598-A-Gchr17-16939598-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012452.3(TNFRSF13B):c.831T>G(p.Ser277Arg) 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. 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. Synonymous variant affecting the same amino acid position (i.e. S277S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TNFRSF13B NM_012452.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875

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]

ACMG classification

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=0.06594628).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF13B	NM_012452.3	c.831T>G	p.Ser277Arg	missense_variant	5/5	ENST00000261652.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF13B	ENST00000261652.7	c.831T>G	p.Ser277Arg	missense_variant	5/5	1	NM_012452.3	P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	0.0026	T
BayesDel_noAF	Benign	-0.23
Cadd	Benign	6.0
Dann	Benign	0.39
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.20	N;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.2	N;.
REVEL	Uncertain	0.34
Sift	Benign	0.058	T;.
Sift4G	Uncertain	0.060	T;T
Polyphen		0.0	B;B
Vest4		0.16
MutPred		0.22		Loss of glycosylation at S277 (P = 0.0028);.;
MVP		0.28
MPC		0.012
ClinPred		0.039	T
GERP RS		-0.34
Varity_R		0.066
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

Other links and lift over

dbSNP: rs11078355; hg19: chr17-16842912;