Variant 8-23137998-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000312584.4(TNFRSF10D):c.1033A>C(p.Thr345Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00446 in 1,614,080 control chromosomes in the GnomAD database, including 274 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.024 ( 155 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 119 hom. )

Consequence

TNFRSF10D
ENST00000312584.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.312

Variant links:

Genes affected

TNFRSF10D (HGNC:11907): (TNF receptor superfamily member 10d) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains an extracellular TRAIL-binding domain, a transmembrane domain, and a truncated cytoplamic death domain. This receptor does not induce apoptosis, and has been shown to play an inhibitory role in TRAIL-induced cell apoptosis. [provided by RefSeq, Jul 2008]

TNFRSF10D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020661056).

BP6

Variant 8-23137998-T-G is Benign according to our data. Variant chr8-23137998-T-G is described in ClinVar as [Benign]. Clinvar id is 776293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10D	NM_003840.5 linkuse as main transcript	c.1033A>C	p.Thr345Pro	missense_variant	9/9	ENST00000312584.4	NP_003831.2	Q9UBN6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF10D	ENST00000312584.4 linkuse as main transcript	c.1033A>C	p.Thr345Pro	missense_variant	9/9	1	NM_003840.5	ENSP00000310263.3		Q9UBN6

Frequencies

GnomAD3 genomes

AF:

0.0241

AC:

3662

AN:

152146

Hom.:

153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0839

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00890

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.00636

AC:

1599

AN:

251284

Hom.:

AF XY:

0.00471

AC XY:

640

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.0884

Gnomad AMR exome

AF:

0.00341

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000211

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00242

AC:

3531

AN:

1461816

Hom.:

119

Cov.:

AF XY:

0.00208

AC XY:

1513

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0837

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000173

Gnomad4 OTH exome

AF:

0.00558

GnomAD4 genome

AF:

0.0241

AC:

3665

AN:

152264

Hom.:

155

Cov.:

AF XY:

0.0233

AC XY:

1738

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0837

Gnomad4 AMR

AF:

0.00889

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.0282

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0831

AC:

366

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00764

AC:

927

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

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	Labcorp Genetics (formerly Invitae), Labcorp	Jun 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.42

CADD

Benign

5.0

DANN

Benign

0.49

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.039

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.9

REVEL

Benign

0.14

Sift

Benign

0.19

Sift4G

Benign

0.075

Vest4

0.19

MVP

0.59

MPC

0.18

ClinPred

0.0029

GERP RS

1.9

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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