Variant 1-173186806-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003326.5(TNFSF4):c.262G>A(p.Val88Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

TNFSF4
NM_003326.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.284

Variant links:

Genes affected

TNFSF4 (HGNC:11934): (TNF superfamily member 4) This gene encodes a cytokine of the tumor necrosis factor (TNF) ligand family. The encoded protein functions in T cell antigen-presenting cell (APC) interactions and mediates adhesion of activated T cells to endothelial cells. Polymorphisms in this gene have been associated with Sjogren's syndrome and systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

TNFSF4 links:

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ACMG classification

Classification made for transcript

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=0.22202054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF4	NM_003326.5 linkuse as main transcript	c.262G>A	p.Val88Met	missense_variant	3/3	ENST00000281834.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF4	ENST00000281834.4 linkuse as main transcript	c.262G>A	p.Val88Met	missense_variant	3/3	1	NM_003326.5	P1	P23510-1
TNFSF4	ENST00000367718.5 linkuse as main transcript	c.112G>A	p.Val38Met	missense_variant	3/3	1			P23510-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248212

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134210

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1460820

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726576

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2022

The c.262G>A (p.V88M) alteration is located in exon 3 (coding exon 3) of the TNFSF4 gene. This alteration results from a G to A substitution at nucleotide position 262, causing the valine (V) at amino acid position 88 to be replaced by a methionine (M). 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

Uncertain

0.48

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Benign

-0.15

Cadd

Benign

Dann

Benign

0.97

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.82

T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.22

T;T

MetaSVM

Uncertain

-0.042

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.0

D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0050

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.50

.;P

Vest4

0.16

MutPred

0.56

.;Loss of methylation at K87 (P = 0.0193);

MVP

0.90

MPC

0.67

ClinPred

0.63

GERP RS

-0.27

Varity_R

0.10

gMVP

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over