3-172506136-T-G

Position:

• chr3-172506136-T-G

Variant summary

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

The NM_003810.4(TNFSF10):​c.*356A>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 0.687 in 186,856 control chromosomes in the GnomAD database, including 44,728 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 (37042 hom., cov: 32)
  • Exomes 𝑓: 0.65 (7686 hom.)
• Consequence: TNFSF10 NM_003810.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF10	NM_003810.4	c.*356A>C		3_prime_UTR_variant	5/5	ENST00000241261.7
TNFSF10	NM_001190942.2	c.*748A>C		3_prime_UTR_variant	3/3
TNFSF10	NR_033994.2	n.1205A>C		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF10	ENST00000241261.7	c.*356A>C		3_prime_UTR_variant	5/5	1	NM_003810.4	P1
TNFSF10	ENST00000420541.6	c.*748A>C		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105500 AN: 151902 Hom.: 37027 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.707

GnomAD4 exome AF: 0.654 AC: 22783 AN: 34836 Hom.: 7686 Cov.: 0 AF XY: 0.652 AC XY: 11804 AN XY: 18092

Gnomad4 AFR exome AF: 0.771

Gnomad4 AMR exome AF: 0.513

Gnomad4 ASJ exome AF: 0.725

Gnomad4 EAS exome AF: 0.588

Gnomad4 SAS exome AF: 0.640

Gnomad4 FIN exome AF: 0.694

Gnomad4 NFE exome AF: 0.663

Gnomad4 OTH exome AF: 0.669

GnomAD4 genome AF: 0.694 AC: 105563 AN: 152020 Hom.: 37042 Cov.: 32 AF XY: 0.692 AC XY: 51399 AN XY: 74322

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.704

Alfa AF: 0.662 Hom.: 9801

Bravo AF: 0.686

Asia WGS AF: 0.649 AC: 2256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.3
DANN	Benign	0.81

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: rs1131542; hg19: chr3-172223926;