chr3-172505351-C-A

Variant names:

• chr3-172505351-C-A
• rs9859259
• NM_003810.4:c.*1141G>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003810.4(TNFSF10):​c.*1141G>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 148,374 control chromosomes in the GnomAD database, including 19,994 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 0.50 (19994 hom., cov: 25)
• Consequence: TNFSF10 NM_003810.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF10	NM_003810.4	c.*1141G>T		downstream_gene_variant		ENST00000241261.7	NP_003801.1
TNFSF10	NM_001190942.2	c.*1533G>T		downstream_gene_variant			NP_001177871.1
TNFSF10	NR_033994.2	n.*157G>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF10	ENST00000241261.7	c.*1141G>T		downstream_gene_variant		1	NM_003810.4	ENSP00000241261.2

Frequencies

GnomAD3 genomes AF: 0.504 AC: 74737 AN: 148270 Hom.: 19979 Cov.: 25

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.403

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.504 AC: 74796 AN: 148374 Hom.: 19994 Cov.: 25 AF XY: 0.499 AC XY: 35995 AN XY: 72128

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.486

Alfa AF: 0.454 Hom.: 7569

Bravo AF: 0.511

Asia WGS AF: 0.534 AC: 1853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9859259; hg19: chr3-172223141;