rs35975099

Variant names:

• chr3-172505416-G-GGTGA
• rs35975099
• NM_003810.4:c.*1075_*1076insTCAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003810.4(TNFSF10):​c.*1075_*1076insTCAC variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,354 control chromosomes in the GnomAD database, including 36,987 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (36987 hom., cov: 0)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: TNFSF10 NM_003810.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.794

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF10	NM_003810.4	c.*1075_*1076insTCAC		downstream_gene_variant		ENST00000241261.7	NP_003801.1
TNFSF10	NM_001190942.2	c.*1467_*1468insTCAC		downstream_gene_variant			NP_001177871.1
TNFSF10	NR_033994.2	n.*91_*92insTCAC		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF10	ENST00000241261.7	c.*1075_*1076insTCAC		downstream_gene_variant		1	NM_003810.4	ENSP00000241261.2
TNFSF10	ENST00000420541.6	c.*1467_*1468insTCAC		downstream_gene_variant		1		ENSP00000389931.2

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105176 AN: 151230 Hom.: 36972 Cov.: 0

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.708

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.695 AC: 105240 AN: 151350 Hom.: 36987 Cov.: 0 AF XY: 0.692 AC XY: 51188 AN XY: 73934

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.631

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.705

Alfa AF: 0.693 Hom.: 3938

Asia WGS AF: 0.650 AC: 2254 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35975099; hg19: chr3-172223206;