rs344560

Positions:

• chr19-6665009-T-A
• chr19-6665009-T-C
• chr19-6665009-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001376887.1(TNFSF14):​c.640A>T​(p.Lys214Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNFSF14 NM_001376887.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF14	NM_001376887.1	c.640A>T	p.Lys214Ter	stop_gained	4/4	ENST00000675206.1
TNFSF14	NM_003807.5	c.640A>T	p.Lys214Ter	stop_gained	5/5
TNFSF14	NM_172014.3	c.532A>T	p.Lys178Ter	stop_gained	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF14	ENST00000675206.1	c.640A>T	p.Lys214Ter	stop_gained	4/4		NM_001376887.1	P1
TNFSF14	ENST00000599359.1	c.640A>T	p.Lys214Ter	stop_gained	5/5	1		P1
TNFSF14	ENST00000245912.7	c.532A>T	p.Lys178Ter	stop_gained	4/4	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 78

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.55
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Benign	0.11
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.079	N
MutationTaster	Benign	1.0	D;D
Vest4		0.28
GERP RS		2.3

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

Other links and lift over

dbSNP: rs344560; hg19: chr19-6665020;