3-172506513-A-G

Variant names:

• chr3-172506513-A-G
• rs1131532
• NM_003810.4:c.825T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003810.4(TNFSF10):​c.825T>C​(p.Phe275Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 1,603,922 control chromosomes in the GnomAD database, including 365,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (36926 hom., cov: 32)
  • Exomes 𝑓: 0.67 (328304 hom.)
• Consequence: TNFSF10 NM_003810.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.430
• Publications: 31 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-172506513-A-G is Benign according to our data. Variant chr3-172506513-A-G is described in ClinVar as Benign. ClinVar VariationId is 1236214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	NM_003810.4	MANE Select	c.825T>C	p.Phe275Phe	synonymous	Exon 5 of 5	NP_003801.1
	TNFSF10	NR_033994.2		n.828T>C		non_coding_transcript_exon	Exon 4 of 4
	TNFSF10	NM_001190942.2		c.*371T>C		3_prime_UTR	Exon 3 of 3	NP_001177871.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	ENST00000241261.7	TSL:1 MANE Select	c.825T>C	p.Phe275Phe	synonymous	Exon 5 of 5	ENSP00000241261.2
	TNFSF10	ENST00000420541.6	TSL:1	c.*371T>C		3_prime_UTR	Exon 3 of 3	ENSP00000389931.2

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105355 AN: 151980 Hom.: 36913 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.707

GnomAD2 exomes AF: 0.654 AC: 158359 AN: 242212 AF XY: 0.659

Gnomad AFR exome AF: 0.780

Gnomad AMR exome AF: 0.469

Gnomad ASJ exome AF: 0.735

Gnomad EAS exome AF: 0.605

Gnomad FIN exome AF: 0.713

Gnomad NFE exome AF: 0.681

Gnomad OTH exome AF: 0.676

GnomAD4 exome AF: 0.670 AC: 973361 AN: 1451824 Hom.: 328304 Cov.: 61 AF XY: 0.670 AC XY: 483876 AN XY: 721766

African (AFR) AF: 0.783 AC: 25672 AN: 32796

American (AMR) AF: 0.480 AC: 20246 AN: 42182

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 18795 AN: 25566

East Asian (EAS) AF: 0.603 AC: 23892 AN: 39626

South Asian (SAS) AF: 0.636 AC: 53335 AN: 83800

European-Finnish (FIN) AF: 0.712 AC: 37924 AN: 53250

Middle Eastern (MID) AF: 0.761 AC: 4345 AN: 5712

European-Non Finnish (NFE) AF: 0.675 AC: 748118 AN: 1108926

Other (OTH) AF: 0.684 AC: 41034 AN: 59966

GnomAD4 genome AF: 0.693 AC: 105417 AN: 152098 Hom.: 36926 Cov.: 32 AF XY: 0.690 AC XY: 51339 AN XY: 74370

African (AFR) AF: 0.775 AC: 32141 AN: 41484

American (AMR) AF: 0.567 AC: 8658 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2519 AN: 3472

East Asian (EAS) AF: 0.609 AC: 3150 AN: 5176

South Asian (SAS) AF: 0.631 AC: 3036 AN: 4814

European-Finnish (FIN) AF: 0.703 AC: 7439 AN: 10588

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

European-Non Finnish (NFE) AF: 0.677 AC: 46042 AN: 67976

Other (OTH) AF: 0.704 AC: 1483 AN: 2108

Alfa AF: 0.640 Hom.: 64559

Bravo AF: 0.685

EpiCase AF: 0.691

EpiControl AF: 0.697

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.19
DANN	Benign	0.42
PhyloP100		-0.43
Mutation Taster		=95/5	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: rs1131532; hg19: chr3-172224303; COSMIC: COSV53842647; COSMIC: COSV53842647;