3-172505830-A-G

Variant names:

• chr3-172505830-A-G
• rs1131580
• NM_003810.4:c.*662T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003810.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	NM_003810.4	MANE Select	c.*662T>C		3_prime_UTR	Exon 5 of 5	NP_003801.1
	TNFSF10	NM_001190942.2		c.*1054T>C		3_prime_UTR	Exon 3 of 3	NP_001177871.1
	TNFSF10	NR_033994.2		n.1511T>C		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	ENST00000241261.7	TSL:1 MANE Select	c.*662T>C		3_prime_UTR	Exon 5 of 5	ENSP00000241261.2
	TNFSF10	ENST00000420541.6	TSL:1	c.*1054T>C		3_prime_UTR	Exon 3 of 3	ENSP00000389931.2
	TNFSF10	ENST00000855870.1		c.*662T>C		3_prime_UTR	Exon 5 of 5	ENSP00000525929.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.760 AC: 38 AN: 50

Other (OTH) AF: 1.00 AC: 2 AN: 2

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

African (AFR) AF: 0.778 AC: 32008 AN: 41138

American (AMR) AF: 0.569 AC: 8633 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2514 AN: 3458

East Asian (EAS) AF: 0.633 AC: 3227 AN: 5096

South Asian (SAS) AF: 0.636 AC: 3048 AN: 4790

European-Finnish (FIN) AF: 0.702 AC: 7256 AN: 10340

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 45885 AN: 67784

Other (OTH) AF: 0.703 AC: 1467 AN: 2088

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.40
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1131580; hg19: chr3-172223620;