Variant chr3-172506513-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003810.4(TNFSF10):c.825T>C(p.Phe275=) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.430

Variant links:

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]

TNFSF10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TNFSF10	NM_003810.4 linkuse as main transcript	c.825T>C	p.Phe275=	synonymous_variant	5/5	ENST00000241261.7	NP_003801.1
TNFSF10	NM_001190942.2 linkuse as main transcript	c.*371T>C		3_prime_UTR_variant	3/3		NP_001177871.1
TNFSF10	NR_033994.2 linkuse as main transcript	n.828T>C		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF10	ENST00000241261.7 linkuse as main transcript	c.825T>C	p.Phe275=	synonymous_variant	5/5	1	NM_003810.4	ENSP00000241261	P1	P50591-1
TNFSF10	ENST00000420541.6 linkuse as main transcript	c.*371T>C		3_prime_UTR_variant	3/3	1		ENSP00000389931		P50591-2

Frequencies

GnomAD3 genomes

AF:

0.693

AC:

105355

AN:

151980

Hom.:

36913

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.654

AC:

158359

AN:

242212

Hom.:

52672

AF XY:

0.659

AC XY:

86211

AN XY:

130798

show subpopulations

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 SAS exome

AF:

0.639

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.:

AF XY:

0.670

AC XY:

483876

AN XY:

721766

show subpopulations

Gnomad4 AFR exome

AF:

0.783

Gnomad4 AMR exome

AF:

0.480

Gnomad4 ASJ exome

AF:

0.735

Gnomad4 EAS exome

AF:

0.603

Gnomad4 SAS exome

AF:

0.636

Gnomad4 FIN exome

AF:

0.712

Gnomad4 NFE exome

AF:

0.675

Gnomad4 OTH exome

AF:

0.684

GnomAD4 genome

AF:

0.693

AC:

105417

AN:

152098

Hom.:

36926

Cov.:

AF XY:

0.690

AC XY:

51339

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.775

Gnomad4 AMR

AF:

0.567

Gnomad4 ASJ

AF:

0.726

Gnomad4 EAS

AF:

0.609

Gnomad4 SAS

AF:

0.631

Gnomad4 FIN

AF:

0.703

Gnomad4 NFE

AF:

0.677

Gnomad4 OTH

AF:

0.704

Alfa

AF:

0.663

Hom.:

18956

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.19

DANN

Benign

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over