NM_003808.4:c.*263C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003808.4(TNFSF13):c.*263C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,596,328 control chromosomes in the GnomAD database, including 21,925 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1890 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20035 hom. )

Consequence

TNFSF13
NM_003808.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.272

Publications

34 publications found

Variant links:

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]

TNFSF13 links:

TNFSF12-TNFSF13 (HGNC:33537): (TNFSF12-TNFSF13 readthrough) This gene encodes a member of the tumor necrosis factor superfamily. It encodes a hybrid protein composed of the cytoplasmic and transmembrane domains of family member 12 fused to the C-terminal domain of family member 13. The hybrid protein is membrane anchored and presents the receptor-binding domain of family member 13 at the cell surface. It stimulates cycling in T- and B-lymphoma cell lines. [provided by RefSeq, Jul 2008]

TNFSF12-TNFSF13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 17-7561096-C-T is Benign according to our data. Variant chr17-7561096-C-T is described in ClinVar as Benign. ClinVar VariationId is 1230540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003808.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TNFSF13	NM_003808.4	MANE Select	c.*263C>T	3_prime_UTR	Exon 6 of 6	NP_003799.1
TNFSF13	NR_073490.3		n.1179C>T	non_coding_transcript_exon	Exon 4 of 4
TNFSF12-TNFSF13	NM_172089.4		c.*263C>T	3_prime_UTR	Exon 11 of 11	NP_742086.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TNFSF13	ENST00000338784.9	TSL:1 MANE Select	c.*263C>T	3_prime_UTR	Exon 6 of 6	ENSP00000343505.4
TNFSF12-TNFSF13	ENST00000293826.4	TSL:1	c.*263C>T	3_prime_UTR	Exon 11 of 11	ENSP00000293826.4
TNFSF13	ENST00000396545.4	TSL:1	c.*91C>T	3_prime_UTR	Exon 7 of 7	ENSP00000379794.4

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23110

AN:

151874

Hom.:

1881

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.165

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.0523

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.0644

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.144

GnomAD4 exome

AF:

0.163

AC:

235850

AN:

1444336

Hom.:

20035

Cov.:

AF XY:

0.162

AC XY:

116430

AN XY:

719328

show subpopulations

African (AFR)

AF:

0.175

AC:

5800

AN:

33056

American (AMR)

AF:

0.100

AC:

4452

AN:

44510

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

4754

AN:

25824

East Asian (EAS)

AF:

0.0717

AC:

2841

AN:

39596

South Asian (SAS)

AF:

0.146

AC:

12527

AN:

85698

European-Finnish (FIN)

AF:

0.0774

AC:

4015

AN:

51890

Middle Eastern (MID)

AF:

0.119

AC:

682

AN:

5722

European-Non Finnish (NFE)

AF:

0.174

AC:

190898

AN:

1098248

Other (OTH)

AF:

0.165

AC:

9881

AN:

59792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

10477

20953

31430

41906

52383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6826

13652

20478

27304

34130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.152

AC:

23137

AN:

151992

Hom.:

1890

Cov.:

AF XY:

0.146

AC XY:

10876

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.174

AC:

7194

AN:

41378

American (AMR)

AF:

0.126

AC:

1927

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

647

AN:

3468

East Asian (EAS)

AF:

0.0524

AC:

271

AN:

5170

South Asian (SAS)

AF:

0.157

AC:

759

AN:

4822

European-Finnish (FIN)

AF:

0.0644

AC:

683

AN:

10600

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.164

AC:

11178

AN:

67954

Other (OTH)

AF:

0.146

AC:

308

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

977

1954

2932

3909

4886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.160

Hom.:

3759

Bravo

AF:

0.158

Asia WGS

AF:

0.146

AC:

509

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 27% of patients studied by a panel of primary immunodeficiencies. Number of patients: 26. Only high quality variants are reported.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over