17-7559152-C-T

Variant names:

• chr17-7559152-C-T
• rs142987696
• NM_003808.4:c.113C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003808.4(TNFSF13):​c.113C>T​(p.Ala38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000416 in 1,612,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00044 (0 hom.)
• Consequence: TNFSF13 NM_003808.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040907502).

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.113C>T	p.Ala38Val	missense	Exon 1 of 6	NP_003799.1	O75888-1
	TNFSF13	NM_172088.4		c.113C>T	p.Ala38Val	missense	Exon 1 of 7	NP_742085.1	O75888-3
	TNFSF13	NM_172087.3		c.113C>T	p.Ala38Val	missense	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.113C>T	p.Ala38Val	missense	Exon 1 of 6	ENSP00000343505.4	O75888-1
	TNFSF13	ENST00000396545.4	TSL:1	c.113C>T	p.Ala38Val	missense	Exon 1 of 7	ENSP00000379794.4	O75888-3
	TNFSF13	ENST00000349228.8	TSL:1	c.113C>T	p.Ala38Val	missense	Exon 1 of 5	ENSP00000314455.6	O75888-2

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152198 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000259 AC: 64 AN: 246894 AF XY: 0.000282

Gnomad AFR exome AF: 0.000339

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000413

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000438 AC: 639 AN: 1460296 Hom.: 0 Cov.: 30 AF XY: 0.000453 AC XY: 329 AN XY: 726242

African (AFR) AF: 0.000149 AC: 5 AN: 33460

American (AMR) AF: 0.000381 AC: 17 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53038

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.000537 AC: 597 AN: 1111174

Other (OTH) AF: 0.000332 AC: 20 AN: 60296

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152316 Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 16 AN XY: 74474

African (AFR) AF: 0.0000721 AC: 3 AN: 41584

American (AMR) AF: 0.000196 AC: 3 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68028

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000295 Hom.: 0

Bravo AF: 0.000215

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000230 AC: 1

ESP6500EA AF: 0.000351 AC: 3

ExAC AF: 0.000190 AC: 23

EpiCase AF: 0.000709

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.041	T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Benign	1.2	L
PhyloP100		1.0
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.15
Sift	Benign	0.19	T
Sift4G	Benign	0.67	T
Polyphen		0.012	B
Vest4		0.19
MVP		0.70
MPC		0.34
ClinPred		0.022	T
GERP RS		2.8
PromoterAI		-0.038	Neutral
Varity_R		0.041
gMVP		0.33
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs142987696; hg19: chr17-7462469;