3-172510754-G-T

Variant names:

• chr3-172510754-G-T
• rs3136597
• NM_003810.4:c.313+863C>A

Variant summary

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

The NM_003810.4(TNFSF10):​c.313+863C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,608 control chromosomes in the GnomAD database, including 6,579 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 0.27 (6579 hom., cov: 31)
• Consequence: TNFSF10 NM_003810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303
• Publications: 20 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	NM_003810.4	MANE Select	c.313+863C>A		intron	N/A	NP_003801.1
	TNFSF10	NM_001190942.2		c.271-3835C>A		intron	N/A	NP_001177871.1
	TNFSF10	NR_033994.2		n.317-1433C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	ENST00000241261.7	TSL:1 MANE Select	c.313+863C>A		intron	N/A	ENSP00000241261.2
	TNFSF10	ENST00000420541.6	TSL:1	c.271-3835C>A		intron	N/A	ENSP00000389931.2
	TNFSF10	ENST00000430881.1	TSL:5	n.196-1433C>A		intron	N/A	ENSP00000404008.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40940 AN: 151490 Hom.: 6571 Cov.: 31

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.0637

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.270 AC: 40979 AN: 151608 Hom.: 6579 Cov.: 31 AF XY: 0.261 AC XY: 19306 AN XY: 74062

African (AFR) AF: 0.459 AC: 18937 AN: 41260

American (AMR) AF: 0.208 AC: 3158 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 701 AN: 3466

East Asian (EAS) AF: 0.0640 AC: 331 AN: 5170

South Asian (SAS) AF: 0.106 AC: 511 AN: 4802

European-Finnish (FIN) AF: 0.148 AC: 1551 AN: 10498

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15131 AN: 67928

Other (OTH) AF: 0.259 AC: 543 AN: 2098

Alfa AF: 0.232 Hom.: 20034

Bravo AF: 0.284

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.94
DANN	Benign	0.64
PhyloP100		-0.30
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: rs3136597; hg19: chr3-172228544;