17-16939598-A-C

Variant names:

• chr17-16939598-A-C
• rs11078355
• NM_012452.3:c.831T>G

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 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
• Publications: 25 publications found

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

ENSG00000307457 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06594628).

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	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF13B	NM_012452.3	MANE Select	c.831T>G	p.Ser277Arg	missense	Exon 5 of 5	NP_036584.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF13B	ENST00000261652.7	TSL:1 MANE Select	c.831T>G	p.Ser277Arg	missense	Exon 5 of 5	ENSP00000261652.2
	TNFRSF13B	ENST00000583789.1	TSL:1	c.693T>G	p.Ser231Arg	missense	Exon 4 of 4	ENSP00000462952.1
	TNFRSF13B	ENST00000579009.1	TSL:6	n.1465T>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.20	N
PhyloP100		-0.88
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.34
Sift	Benign	0.058	T
Sift4G	Uncertain	0.060	T
Polyphen		0.0	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

Other links and lift over

dbSNP: rs11078355; hg19: chr17-16842912;