17-7557242-G-C

Variant names:

• chr17-7557242-G-C
• NM_003809.3:c.642G>C
• TNFSF12 p.Gly214Gly

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003809.3(TNFSF12):​c.642G>C​(p.Gly214Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G214G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNFSF12 NM_003809.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=1.13 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003809.3. 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
	TNFSF12	NM_003809.3	MANE Select	c.642G>C	p.Gly214Gly	synonymous	Exon 7 of 7	NP_003800.1	O43508-1
	TNFSF12-TNFSF13	NM_172089.4		c.498+340G>C		intron	N/A	NP_742086.1	A0A0A6YY99
	TNFSF12	NR_037146.2		n.977G>C		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF12	ENST00000293825.11	TSL:1 MANE Select	c.642G>C	p.Gly214Gly	synonymous	Exon 7 of 7	ENSP00000293825.6	O43508-1
	TNFSF12-TNFSF13	ENST00000293826.4	TSL:1	c.498+340G>C		intron	N/A	ENSP00000293826.4
	TNFSF12	ENST00000322272.11	TSL:1	n.*476G>C		non_coding_transcript_exon	Exon 8 of 8	ENSP00000314636.7	C0H5Y4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 68

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.0
PhyloP100		1.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-7460559;