rs3803800

chr17-7559652-A-Gchr17-7559652-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003808.4(TNFSF13):c.287A>G(p.Asn96Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 1,612,798 control chromosomes in the GnomAD database, including 458,477 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.64 (33846 hom., cov: 28)
  • Exomes 𝑓: 0.76 (424631 hom.)
• Consequence: TNFSF13 NM_003808.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.14

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2001234E-6).
• BP6: Variant 17-7559652-A-G is Benign according to our data. Variant chr17-7559652-A-G is described in ClinVar as [Benign]. Clinvar id is 1270041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF13	NM_003808.4	c.287A>G	p.Asn96Ser	missense_variant	2/6	ENST00000338784.9
TNFSF12-TNFSF13	NM_172089.4	c.527A>G	p.Asn176Ser	missense_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF13	ENST00000338784.9	c.287A>G	p.Asn96Ser	missense_variant	2/6	1	NM_003808.4	P3

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97085 AN: 151520 Hom.: 33838 Cov.: 28

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.676

GnomAD3 exomes AF: 0.696 AC: 172329 AN: 247674 Hom.: 61948 AF XY: 0.710 AC XY: 95181 AN XY: 134044

Gnomad AFR exome AF: 0.346

Gnomad AMR exome AF: 0.564

Gnomad ASJ exome AF: 0.796

Gnomad EAS exome AF: 0.631

Gnomad SAS exome AF: 0.661

Gnomad FIN exome AF: 0.754

Gnomad NFE exome AF: 0.785

Gnomad OTH exome AF: 0.743

GnomAD4 exome AF: 0.757 AC: 1106534 AN: 1461160 Hom.: 424631 Cov.: 82 AF XY: 0.757 AC XY: 549960 AN XY: 726822

Gnomad4 AFR exome AF: 0.343

Gnomad4 AMR exome AF: 0.573

Gnomad4 ASJ exome AF: 0.795

Gnomad4 EAS exome AF: 0.668

Gnomad4 SAS exome AF: 0.662

Gnomad4 FIN exome AF: 0.756

Gnomad4 NFE exome AF: 0.788

Gnomad4 OTH exome AF: 0.731

GnomAD4 genome AF: 0.640 AC: 97123 AN: 151638 Hom.: 33846 Cov.: 28 AF XY: 0.641 AC XY: 47498 AN XY: 74074

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.793

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.787

Gnomad4 OTH AF: 0.669

Alfa AF: 0.760 Hom.: 109469

Bravo AF: 0.620

TwinsUK AF: 0.795 AC: 2949

ALSPAC AF: 0.800 AC: 3085

ESP6500AA AF: 0.377 AC: 1663

ESP6500EA AF: 0.785 AC: 6749

ExAC AF: 0.694 AC: 84245

Asia WGS AF: 0.569 AC: 1979 AN: 3478

EpiCase AF: 0.799

EpiControl AF: 0.796

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 80% of patients studied by a panel of primary immunodeficiencies. Number of patients: 76. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

This variant is associated with the following publications: (PMID: 22864923) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	13
Dann	Benign	0.96
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.71	T;T;T;T;T;T
MetaRNN	Benign	0.0000012	T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.47	N;N;N;N;N;N
REVEL	Benign	0.29
Sift	Benign	0.33	T;T;T;T;T;T
Sift4G	Benign	0.48	T;T;T;T;T;T
Polyphen		0.0020, 0.0, 0.0010	.;.;.;B;B;B
Vest4		0.026
MPC		0.45
ClinPred		0.0084	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.040
gMVP		0.070

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs3803800; hg19: chr17-7462969; COSMIC: COSV53432713; COSMIC: COSV53432713;