3-172505837-T-C

Position:

• chr3-172505837-T-C

Variant summary

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

The NM_003810.4(TNFSF10):​c.*655A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,208 control chromosomes in the GnomAD database, including 36,907 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 (36907 hom., cov: 28)
  • Exomes 𝑓: 0.69 (19 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNFSF10 NM_003810.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF10	NM_003810.4	c.*655A>G		3_prime_UTR_variant	5/5	ENST00000241261.7	NP_003801.1
TNFSF10	NM_001190942.2	c.*1047A>G		3_prime_UTR_variant	3/3		NP_001177871.1
TNFSF10	NR_033994.2	n.1504A>G		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF10	ENST00000241261.7	c.*655A>G		3_prime_UTR_variant	5/5	1	NM_003810.4	ENSP00000241261	P1
TNFSF10	ENST00000420541.6	c.*1047A>G		3_prime_UTR_variant	3/3	1		ENSP00000389931

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105042 AN: 151090 Hom.: 36892 Cov.: 28

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.706

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.694 AC: 50 AN: 72 Hom.: 19 Cov.: 0 AF XY: 0.635 AC XY: 33 AN XY: 52

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.703

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.695 AC: 105105 AN: 151208 Hom.: 36907 Cov.: 28 AF XY: 0.692 AC XY: 51082 AN XY: 73818

Gnomad4 AFR AF: 0.778

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.703

Alfa AF: 0.689 Hom.: 4525

Bravo AF: 0.687

Asia WGS AF: 0.651 AC: 2263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.0
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs1131579; hg19: chr3-172223627;