Variant chr8-23144475-A-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 NM_003840.5(TNFRSF10D):c.929T>C(p.Leu310Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,613,742 control chromosomes in the GnomAD database, including 314,888 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 0.62 ( 29133 hom., cov: 32)

Exomes 𝑓: 0.62 ( 285755 hom. )

Consequence

TNFRSF10D
NM_003840.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.45

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=7.7405576E-7).

BP6

Variant 8-23144475-A-G is Benign according to our data. Variant chr8-23144475-A-G is described in ClinVar as [Benign]. Clinvar id is 1263607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 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.929T>C	p.Leu310Ser	missense_variant	7/9	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.929T>C	p.Leu310Ser	missense_variant	7/9	1	NM_003840.5	ENSP00000310263.3		Q9UBN6

Frequencies

GnomAD3 genomes

AF:

0.615

AC:

93505

AN:

151954

Hom.:

29099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.555

Gnomad AMI

AF:

0.516

Gnomad AMR

AF:

0.707

Gnomad ASJ

AF:

0.568

Gnomad EAS

AF:

0.915

Gnomad SAS

AF:

0.744

Gnomad FIN

AF:

0.603

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.604

Gnomad OTH

AF:

0.646

GnomAD3 exomes

AF:

0.658

AC:

165136

AN:

250868

Hom.:

55589

AF XY:

0.658

AC XY:

89226

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.560

Gnomad AMR exome

AF:

0.758

Gnomad ASJ exome

AF:

0.558

Gnomad EAS exome

AF:

0.901

Gnomad SAS exome

AF:

0.728

Gnomad FIN exome

AF:

0.602

Gnomad NFE exome

AF:

0.603

Gnomad OTH exome

AF:

0.657

GnomAD4 exome

AF:

0.622

AC:

908474

AN:

1461670

Hom.:

285755

Cov.:

AF XY:

0.624

AC XY:

453875

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.556

Gnomad4 AMR exome

AF:

0.755

Gnomad4 ASJ exome

AF:

0.564

Gnomad4 EAS exome

AF:

0.930

Gnomad4 SAS exome

AF:

0.724

Gnomad4 FIN exome

AF:

0.602

Gnomad4 NFE exome

AF:

0.601

Gnomad4 OTH exome

AF:

0.634

GnomAD4 genome

AF:

0.615

AC:

93592

AN:

152072

Hom.:

29133

Cov.:

AF XY:

0.621

AC XY:

46125

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.556

Gnomad4 AMR

AF:

0.708

Gnomad4 ASJ

AF:

0.568

Gnomad4 EAS

AF:

0.916

Gnomad4 SAS

AF:

0.742

Gnomad4 FIN

AF:

0.603

Gnomad4 NFE

AF:

0.604

Gnomad4 OTH

AF:

0.650

Alfa

AF:

0.615

Hom.:

73863

Bravo

AF:

0.621

TwinsUK

AF:

0.604

AC:

2239

ALSPAC

AF:

0.601

AC:

2317

ESP6500AA

AF:

0.562

AC:

2477

ESP6500EA

AF:

0.601

AC:

5170

ExAC

AF:

0.652

AC:

79113

Asia WGS

AF:

0.835

AC:

2902

AN:

3478

EpiCase

AF:

0.603

EpiControl

AF:

0.601

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	clinical testing	GeneDx	Feb 26, 2021	This variant is associated with the following publications: (PMID: 25264005) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.011

DANN

Benign

0.14

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0032

MetaRNN

Benign

7.7e-7

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.31

PROVEAN

Benign

2.8

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.012

MPC

0.18

ClinPred

0.014

GERP RS

-0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.038

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