3-172509683-T-G

Variant names:

• chr3-172509683-T-G
• rs3181143
• NM_003810.4:c.314-362A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003810.4(TNFSF10):​c.314-362A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,134 control chromosomes in the GnomAD database, including 37,687 homozygotes. 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: 𝑓 0.70 (37687 hom., cov: 32)
• Consequence: TNFSF10 NM_003810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 7 publications found

Genes affected

TNFSF10 (HGNC:11925): (TNF superfamily member 10) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein preferentially induces apoptosis in transformed and tumor cells, but does not appear to kill normal cells although it is expressed at a significant level in most normal tissues. This protein binds to several members of TNF receptor superfamily including TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and possibly also to TNFRSF11B/OPG. The activity of this protein may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and TNFRSF11B/OPG that cannot induce apoptosis. The binding of this protein to its receptors has been shown to trigger the activation of MAPK8/JNK, caspase 8, and caspase 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003810.4. 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
	TNFSF10	NM_003810.4	MANE Select	c.314-362A>C		intron	N/A	NP_003801.1	Q6IBA9
	TNFSF10	NM_001190942.2		c.271-2764A>C		intron	N/A	NP_001177871.1	P50591-2
	TNFSF10	NR_033994.2		n.317-362A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	ENST00000241261.7	TSL:1 MANE Select	c.314-362A>C		intron	N/A	ENSP00000241261.2	P50591-1
	TNFSF10	ENST00000420541.6	TSL:1	c.271-2764A>C		intron	N/A	ENSP00000389931.2	P50591-2
	TNFSF10	ENST00000855872.1		c.416-362A>C		intron	N/A	ENSP00000525931.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106522 AN: 152014 Hom.: 37666 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.712

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.701 AC: 106594 AN: 152134 Hom.: 37687 Cov.: 32 AF XY: 0.699 AC XY: 51954 AN XY: 74370

African (AFR) AF: 0.776 AC: 32224 AN: 41508

American (AMR) AF: 0.585 AC: 8939 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2518 AN: 3468

East Asian (EAS) AF: 0.728 AC: 3782 AN: 5192

South Asian (SAS) AF: 0.637 AC: 3079 AN: 4830

European-Finnish (FIN) AF: 0.703 AC: 7410 AN: 10544

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 46202 AN: 67998

Other (OTH) AF: 0.709 AC: 1494 AN: 2108

Alfa AF: 0.604 Hom.: 1894

Bravo AF: 0.694

Asia WGS AF: 0.683 AC: 2374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.57
DANN	Benign	0.72
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3181143; hg19: chr3-172227473;