Variant rs2291667 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001376887.1(TNFSF14):c.95C>T(p.Ser32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000707 in 1,614,132 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00098 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00068 ( 5 hom. )

Consequence

TNFSF14
NM_001376887.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.182

Variant links:

Genes affected

TNFSF14 (HGNC:11930): (TNF superfamily member 14) The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF14, which is a member of the tumor necrosis factor receptor superfamily, and which is also known as a herpesvirus entry mediator (HVEM). This protein may function as a costimulatory factor for the activation of lymphoid cells and as a deterrent to infection by herpesvirus. This protein has been shown to stimulate the proliferation of T cells, and trigger apoptosis of various tumor cells. This protein is also reported to prevent tumor necrosis factor alpha mediated apoptosis in primary hepatocyte. Two alternatively spliced transcript variant encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

TNFSF14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007429868).

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TNFSF14	NM_001376887.1 linkuse as main transcript	c.95C>T	p.Ser32Leu	missense_variant	1/4	ENST00000675206.1	NP_001363816.1
TNFSF14	NM_003807.5 linkuse as main transcript	c.95C>T	p.Ser32Leu	missense_variant	2/5		NP_003798.2
TNFSF14	NM_172014.3 linkuse as main transcript	c.95C>T	p.Ser32Leu	missense_variant	1/4		NP_742011.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF14	ENST00000675206.1 linkuse as main transcript	c.95C>T	p.Ser32Leu	missense_variant	1/4		NM_001376887.1	ENSP00000502837	P1	O43557-1
TNFSF14	ENST00000599359.1 linkuse as main transcript	c.95C>T	p.Ser32Leu	missense_variant	2/5	1		ENSP00000469049	P1	O43557-1
TNFSF14	ENST00000245912.7 linkuse as main transcript	c.95C>T	p.Ser32Leu	missense_variant	1/4	1		ENSP00000245912		O43557-2

Frequencies

GnomAD3 genomes

AF:

0.000986

AC:

150

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00559

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00801

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00156

AC:

393

AN:

251432

Hom.:

AF XY:

0.00156

AC XY:

212

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00810

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00735

Gnomad NFE exome

AF:

0.000466

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000679

AC:

992

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000666

AC XY:

484

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00172

Gnomad4 EAS exome

AF:

0.00652

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00788

Gnomad4 NFE exome

AF:

0.000175

Gnomad4 OTH exome

AF:

0.000811

GnomAD4 genome

AF:

0.000979

AC:

149

AN:

152240

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00541

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.00801

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000472

Hom.:

Bravo

AF:

0.000540

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00142

AC:

172

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.47

.;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.0089

MetaRNN

Benign

0.0074

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.87

N;.

REVEL

Benign

0.046

Sift

Benign

0.31

T;.

Sift4G

Benign

0.13

T;T

Polyphen

0.014

B;B

Vest4

0.16

MVP

0.20

MPC

0.30

ClinPred

0.011

GERP RS

1.4

Varity_R

0.048

gMVP

0.20

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over