3-172505830-A-G

Position:

• chr3-172505830-A-G

Variant summary

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

The NM_003810.4(TNFSF10):​c.*662T>C 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 151,064 control chromosomes in the GnomAD database, including 36,860 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 0.69 (36860 hom., cov: 27)
  • Exomes 𝑓: 0.75 (18 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNFSF10 NM_003810.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792

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=-1.02).
• 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	UniProt
TNFSF10	NM_003810.4	c.*662T>C		3_prime_UTR_variant	5/5	ENST00000241261.7
TNFSF10	NM_001190942.2	c.*1054T>C		3_prime_UTR_variant	3/3
TNFSF10	NR_033994.2	n.1511T>C		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF10	ENST00000241261.7	c.*662T>C		3_prime_UTR_variant	5/5	1	NM_003810.4	P1
TNFSF10	ENST00000420541.6	c.*1054T>C		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.695 AC: 104918 AN: 150946 Hom.: 36845 Cov.: 27

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.706

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.750 AC: 42 AN: 56 Hom.: 18 Cov.: 0 AF XY: 0.694 AC XY: 25 AN XY: 36

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.760

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.695 AC: 104981 AN: 151064 Hom.: 36860 Cov.: 27 AF XY: 0.692 AC XY: 51025 AN XY: 73744

Gnomad4 AFR AF: 0.778

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.703

Alfa AF: 0.684 Hom.: 4213

Bravo AF: 0.687

Asia WGS AF: 0.652 AC: 2265 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	2.9
DANN	Benign	0.40

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: rs1131580; hg19: chr3-172223620;