Variant 8-23191779-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003844.4(TNFRSF10A):c.1322G>A(p.Arg441Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 1,614,030 control chromosomes in the GnomAD database, including 598,025 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.86 ( 56528 hom., cov: 31)

Exomes 𝑓: 0.86 ( 541497 hom. )

Consequence

TNFRSF10A
NM_003844.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0950

Variant links:

Genes affected

TNFRSF10A (HGNC:11904): (TNF receptor superfamily member 10a) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL), and thus transduces cell death signal and induces cell apoptosis. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein. [provided by RefSeq, Jul 2008]

TNFRSF10A links:

TNFRSF10A (HGNC:):

TNFRSF10A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.6099135E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10A	NM_003844.4 linkuse as main transcript	c.1322G>A	p.Arg441Lys	missense_variant	10/10	ENST00000221132.8	NP_003835.3	O00220

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TNFRSF10A	ENST00000221132.8 linkuse as main transcript	c.1322G>A	p.Arg441Lys	missense_variant	10/10	1	NM_003844.4	ENSP00000221132.3	O00220
TNFRSF10A	ENST00000613472.1 linkuse as main transcript	c.848G>A	p.Arg283Lys	missense_variant	9/9	1		ENSP00000480778.1	F8U8C0
TNFRSF10A	ENST00000519862.1 linkuse as main transcript	n.*35G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.861

AC:

130891

AN:

152030

Hom.:

56471

Cov.:

show subpopulations

Gnomad AFR

AF:

0.865

Gnomad AMI

AF:

0.726

Gnomad AMR

AF:

0.904

Gnomad ASJ

AF:

0.889

Gnomad EAS

AF:

0.979

Gnomad SAS

AF:

0.954

Gnomad FIN

AF:

0.792

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.844

Gnomad OTH

AF:

0.872

GnomAD3 exomes

AF:

0.880

AC:

221372

AN:

251456

Hom.:

97826

AF XY:

0.882

AC XY:

119868

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.862

Gnomad AMR exome

AF:

0.937

Gnomad ASJ exome

AF:

0.891

Gnomad EAS exome

AF:

0.981

Gnomad SAS exome

AF:

0.951

Gnomad FIN exome

AF:

0.800

Gnomad NFE exome

AF:

0.845

Gnomad OTH exome

AF:

0.876

GnomAD4 exome

AF:

0.860

AC:

1257001

AN:

1461882

Hom.:

541497

Cov.:

AF XY:

0.863

AC XY:

627266

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.867

Gnomad4 AMR exome

AF:

0.932

Gnomad4 ASJ exome

AF:

0.895

Gnomad4 EAS exome

AF:

0.986

Gnomad4 SAS exome

AF:

0.951

Gnomad4 FIN exome

AF:

0.804

Gnomad4 NFE exome

AF:

0.846

Gnomad4 OTH exome

AF:

0.870

GnomAD4 genome

AF:

0.861

AC:

131004

AN:

152148

Hom.:

56528

Cov.:

AF XY:

0.861

AC XY:

64034

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.866

Gnomad4 AMR

AF:

0.904

Gnomad4 ASJ

AF:

0.889

Gnomad4 EAS

AF:

0.979

Gnomad4 SAS

AF:

0.954

Gnomad4 FIN

AF:

0.792

Gnomad4 NFE

AF:

0.844

Gnomad4 OTH

AF:

0.874

Alfa

AF:

0.855

Hom.:

142113

Bravo

AF:

0.867

TwinsUK

AF:

0.847

AC:

3142

ALSPAC

AF:

0.844

AC:

3254

ESP6500AA

AF:

0.856

AC:

3773

ESP6500EA

AF:

0.846

AC:

7273

ExAC

AF:

0.878

AC:

106618

Asia WGS

AF:

0.959

AC:

3333

AN:

3478

EpiCase

AF:

0.849

EpiControl

AF:

0.847

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.049

DANN

Benign

0.56

DEOGEN2

Benign

0.064

T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0010

LIST_S2

Benign

0.16

T;T

MetaRNN

Benign

8.6e-7

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.3

N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

1.4

N;.

REVEL

Benign

0.20

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.047

MPC

0.065

ClinPred

0.00023

GERP RS

-2.6

Varity_R

0.035

gMVP

0.41

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over