chr17-7559229-C-A

Variant names:

• chr17-7559229-C-A
• rs759564930
• NM_003808.4:c.190C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003808.4(TNFSF13):​c.190C>A​(p.Arg64Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,514 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: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TNFSF13 NM_003808.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• Publications: 0 publications found

Genes affected

TNFSF13 (HGNC:11928): (TNF superfamily member 13) The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF17/BCMA, a member of the TNF receptor family. This protein and its receptor are both found to be important for B cell development. In vitro experiments suggested that this protein may be able to induce apoptosis through its interaction with other TNF receptor family proteins such as TNFRSF6/FAS and TNFRSF14/HVEM. Alternative splicing results in multiple transcript variants. Some transcripts that skip the last exon of the upstream gene (TNFSF12) and continue into the second exon of this gene have been identified; 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]

ENSG00000276384 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=0.34 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003808.4. 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
	TNFSF13	NM_003808.4	MANE Select	c.190C>A	p.Arg64Arg	synonymous	Exon 1 of 6	NP_003799.1	O75888-1
	TNFSF13	NM_172088.4		c.190C>A	p.Arg64Arg	synonymous	Exon 1 of 7	NP_742085.1	O75888-3
	TNFSF13	NM_172087.3		c.190C>A	p.Arg64Arg	synonymous	Exon 1 of 5	NP_742084.1	O75888-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF13	ENST00000338784.9	TSL:1 MANE Select	c.190C>A	p.Arg64Arg	synonymous	Exon 1 of 6	ENSP00000343505.4	O75888-1
	TNFSF13	ENST00000396545.4	TSL:1	c.190C>A	p.Arg64Arg	synonymous	Exon 1 of 7	ENSP00000379794.4	O75888-3
	TNFSF13	ENST00000349228.8	TSL:1	c.190C>A	p.Arg64Arg	synonymous	Exon 1 of 5	ENSP00000314455.6	O75888-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458514 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 725484

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4640

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111384

Other (OTH) AF: 0.00 AC: 0 AN: 60196

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		0.34
PromoterAI		-0.015	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs759564930; hg19: chr17-7462546;