Variant chr8-23224757-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003844.4(TNFRSF10A):c.305A>C(p.Gln102Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000895 in 1,563,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

TNFRSF10A
NM_003844.4 missense, splice_region

Scores

Splicing: ADA: 0.01030

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.83

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-DT (HGNC:):

TNFRSF10A-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04261583).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10A	NM_003844.4 linkuse as main transcript	c.305A>C	p.Gln102Pro	missense_variant, splice_region_variant	1/10	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.305A>C	p.Gln102Pro	missense_variant, splice_region_variant	1/10	1	NM_003844.4	ENSP00000221132.3	O00220
TNFRSF10A	ENST00000613472.1 linkuse as main transcript	c.31+274A>C		intron_variant		1		ENSP00000480778.1	F8U8C0
TNFRSF10A-DT	ENST00000517774.1 linkuse as main transcript	n.287T>G		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000637

AC:

AN:

1412036

Hom.:

Cov.:

AF XY:

0.00000287

AC XY:

AN XY:

697660

show subpopulations

Gnomad4 AFR exome

AF:

0.000246

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

151918

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000661

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.305A>C (p.Q102P) alteration is located in exon 1 (coding exon 1) of the TNFRSF10A gene. This alteration results from a A to C substitution at nucleotide position 305, causing the glutamine (Q) at amino acid position 102 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.15

DANN

Benign

0.30

DEOGEN2

Benign

0.00083

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.24

M_CAP

Benign

0.0076

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.86

MutationAssessor

Benign

-0.90

PrimateAI

Benign

0.25

PROVEAN

Benign

0.19

REVEL

Benign

0.24

Sift

Benign

0.19

Sift4G

Benign

0.34

Polyphen

0.49

Vest4

0.14

MVP

0.12

MPC

0.10

ClinPred

0.099

GERP RS

-2.5

Varity_R

0.066

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.010

dbscSNV1_RF

Benign

0.31

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