NM_003809.3:c.55G>T

Variant names:

• chr17-7549208-G-T
• NM_003809.3:c.55G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003809.3(TNFSF12):​c.55G>T​(p.Ala19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000842 in 1,187,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: TNFSF12 NM_003809.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95

Genes affected

TNFSF12 (HGNC:11927): (TNF superfamily member 12) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is a ligand for the FN14/TWEAKR receptor. This cytokine has overlapping signaling functions with TNF, but displays a much wider tissue distribution. This cytokine, which exists in both membrane-bound and secreted forms, can induce apoptosis via multiple pathways of cell death in a cell type-specific manner. This cytokine is also found to promote proliferation and migration of endothelial cells, and thus acts as a regulator of angiogenesis. Alternative splicing results in multiple transcript variants. Some transcripts skip the last exon of this gene and continue into the second exon of the neighboring TNFSF13 gene; such read-through transcripts are contained in GeneID 407977, TNFSF12-TNFSF13. [provided by RefSeq, Oct 2010]

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]

ACMG classification

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=0.25575024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF12	NM_003809.3	c.55G>T	p.Ala19Ser	missense_variant	Exon 1 of 7	ENST00000293825.11	NP_003800.1
TNFSF12-TNFSF13	NM_172089.4	c.55G>T	p.Ala19Ser	missense_variant	Exon 1 of 11		NP_742086.1
TNFSF12	NR_037146.2	n.151G>T		non_coding_transcript_exon_variant	Exon 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF12	ENST00000293825.11	c.55G>T	p.Ala19Ser	missense_variant	Exon 1 of 7	1	NM_003809.3	ENSP00000293825.6
TNFSF12-TNFSF13	ENST00000293826.4	c.55G>T	p.Ala19Ser	missense_variant	Exon 1 of 11	1		ENSP00000293826.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.42e-7 AC: 1 AN: 1187182 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 574688

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: 0.00000102

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.78	T;T
M_CAP	Pathogenic	0.50	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Uncertain	0.78	D
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.78	N;N
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.41	T;T
Polyphen		1.0	D;.
Vest4		0.26
MutPred		0.19		Gain of glycosylation at A19 (P = 0.0179);Gain of glycosylation at A19 (P = 0.0179);
MVP		0.56
MPC		0.39
ClinPred		0.91	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.35
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7452525;