17-7559695-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003808.4(TNFSF13):c.330A>C(p.Lys110Asn) 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. 12/21 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)
• Consequence: TNFSF13 NM_003808.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.265

Genes affected

TNFSF13 (HGNC:11928): (TNF superfamily member 13) The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF17/BCMA, a member of the TNF receptor family. This protein and its receptor are both found to be important for B cell development. In vitro experiments suggested that this protein may be able to induce apoptosis through its interaction with other TNF receptor family proteins such as TNFRSF6/FAS and TNFRSF14/HVEM. Alternative splicing results in multiple transcript variants. Some transcripts that skip the last exon of the upstream gene (TNFSF12) and continue into the second exon of this gene have been identified; such read-through transcripts are contained in GeneID 407977, TNFSF12-TNFSF13. [provided by RefSeq, Oct 2010]

TNFSF12-TNFSF13 (HGNC:):

ACMG classification

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=0.15670946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF13	NM_003808.4	c.330A>C	p.Lys110Asn	missense_variant	2/6	ENST00000338784.9
TNFSF12-TNFSF13	NM_172089.4	c.570A>C	p.Lys190Asn	missense_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF13	ENST00000338784.9	c.330A>C	p.Lys110Asn	missense_variant	2/6	1	NM_003808.4	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.570A>C (p.K190N) alteration is located in exon 7 (coding exon 7) of the TNFSF12-TNFSF13 gene. This alteration results from a A to C substitution at nucleotide position 570, causing the lysine (K) at amino acid position 190 to be replaced by an asparagine (N). 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	0.25
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
Cadd	Benign	18
Dann	Uncertain	1.0
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.76	T;T;T;T;T;T
M_CAP	Uncertain	0.29	D
MetaRNN	Benign	0.16	T;T;T;T;T;T
MetaSVM	Uncertain	0.61	D
MutationTaster	Benign	0.82	N;N;D;D;D;D;D;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.23	N;N;N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.039	D;D;D;D;T;T
Sift4G	Uncertain	0.0090	D;T;D;T;T;T
Polyphen		0.0020, 0.95, 0.94	.;.;.;B;P;P
Vest4		0.20
MutPred		0.24		.;.;.;Loss of methylation at K110 (P = 0.0262);Loss of methylation at K110 (P = 0.0262);Loss of methylation at K110 (P = 0.0262);
MVP		0.70
MPC		0.71
ClinPred		0.089	T
GERP RS		0.92
Varity_R		0.065
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7463012;