rs547352394

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_052945.4(TNFRSF13C):c.191G>T(p.Gly64Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,488,228 control chromosomes in the GnomAD database, including 125 homozygotes. 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 Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G64S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0071 ( 6 hom., cov: 32)

Exomes 𝑓: 0.011 ( 119 hom. )

Consequence

TNFRSF13C
NM_052945.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 0.300

Publications

11 publications found

Variant links:

Genes affected

TNFRSF13C (HGNC:17755): (TNF receptor superfamily member 13C) B cell-activating factor (BAFF) enhances B-cell survival in vitro and is a regulator of the peripheral B-cell population. Overexpression of Baff in mice results in mature B-cell hyperplasia and symptoms of systemic lupus erythematosus (SLE). Also, some SLE patients have increased levels of BAFF in serum. Therefore, it has been proposed that abnormally high levels of BAFF may contribute to the pathogenesis of autoimmune diseases by enhancing the survival of autoreactive B cells. The protein encoded by this gene is a receptor for BAFF and is a type III transmembrane protein containing a single extracellular cysteine-rich domain. It is thought that this receptor is the principal receptor required for BAFF-mediated mature B-cell survival. [provided by RefSeq, Jul 2008]

TNFRSF13C Gene-Disease associations (from GenCC):

immunodeficiency, common variable, 4
Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)
common variable immunodeficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TNFRSF13C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050999224).

BP6

Variant 22-41926277-C-A is Benign according to our data. Variant chr22-41926277-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 440343.

BS2

High Homozygotes in GnomAd4 at 6 AD,AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052945.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF13C	NM_052945.4	MANE Select	c.191G>T	p.Gly64Val	missense	Exon 2 of 3	NP_443177.1	Q5H8V1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF13C	ENST00000291232.5	TSL:1 MANE Select	c.191G>T	p.Gly64Val	missense	Exon 2 of 3	ENSP00000291232.3	Q96RJ3-1
	TNFRSF13C	ENST00000898406.1		c.275G>T	p.Gly92Val	missense	Exon 2 of 3	ENSP00000568465.1

Frequencies

GnomAD3 genomes

AF:

0.00714

AC:

1085

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00586

Gnomad MID

AF:

0.0573

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.00765

GnomAD2 exomes

AF:

0.00868

AC:

787

AN:

90680

AF XY:

0.00799

show subpopulations

Gnomad AFR exome

AF:

0.00331

Gnomad AMR exome

AF:

0.00317

Gnomad ASJ exome

AF:

0.00933

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0114

Gnomad NFE exome

AF:

0.0148

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.0107

AC:

14316

AN:

1336076

Hom.:

119

Cov.:

AF XY:

0.0105

AC XY:

6934

AN XY:

658982

show subpopulations

African (AFR)

AF:

0.00257

AC:

AN:

26798

American (AMR)

AF:

0.00286

AC:

AN:

28292

Ashkenazi Jewish (ASJ)

AF:

0.00810

AC:

188

AN:

23204

East Asian (EAS)

AF:

0.00

AC:

AN:

31008

South Asian (SAS)

AF:

0.00242

AC:

178

AN:

73684

European-Finnish (FIN)

AF:

0.0112

AC:

382

AN:

34008

Middle Eastern (MID)

AF:

0.0180

AC:

AN:

4278

European-Non Finnish (NFE)

AF:

0.0121

AC:

12868

AN:

1059360

Other (OTH)

AF:

0.00853

AC:

473

AN:

55444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

742

1484

2227

2969

3711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

494

988

1482

1976

2470

<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:

0.00712

AC:

1083

AN:

152152

Hom.:

Cov.:

AF XY:

0.00646

AC XY:

481

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00193

AC:

AN:

41544

American (AMR)

AF:

0.00203

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00864

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.00207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00586

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.0548

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0119

AC:

810

AN:

67954

Other (OTH)

AF:

0.00757

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

110

164

219

274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0102

Hom.:

Bravo

AF:

0.00642

ExAC

AF:

0.00674

AC:

189

Asia WGS

AF:

0.00117

AC:

AN:

3448

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency, common variable, 4 (4)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.44

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0051

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.30

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.030

Sift

Benign

0.059

Sift4G

Uncertain

0.0070

Polyphen

0.011

Vest4

0.33

MVP

0.043

MPC

2.1

ClinPred

0.044

GERP RS

0.97

Varity_R

0.24

gMVP

0.22

Mutation Taster

=97/3

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over