Variant chr11-73390558-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000064780.7(RELT):c.53C>G(p.Pro18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P18L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Consequence

RELT
ENST00000064780.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.658

Variant links:

Genes affected

RELT (HGNC:13764): (RELT TNF receptor) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is especially abundant in hematologic tissues. It has been shown to activate the NF-kappaB pathway and selectively bind TNF receptor-associated factor 1 (TRAF1). This receptor is capable of stimulating T-cell proliferation in the presence of CD3 signaling, which suggests its regulatory role in immune response. Two alternatively spliced transcript variants of this gene encoding the same protein have been reported. [provided by RefSeq, Jul 2008]

RELT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14515102).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELT	NM_152222.2 linkuse as main transcript	c.53C>G	p.Pro18Arg	missense_variant	3/11	ENST00000064780.7	NP_689408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RELT	ENST00000064780.7 linkuse as main transcript	c.53C>G	p.Pro18Arg	missense_variant	3/11	1	NM_152222.2	ENSP00000064780	P1
RELT	ENST00000393580.2 linkuse as main transcript	c.53C>G	p.Pro18Arg	missense_variant	3/11	1		ENSP00000377207	P1
RELT	ENST00000545687.5 linkuse as main transcript	c.53C>G	p.Pro18Arg	missense_variant	5/7	4		ENSP00000439352
RELT	ENST00000544075.5 linkuse as main transcript	c.53C>G	p.Pro18Arg	missense_variant, NMD_transcript_variant	3/6	3		ENSP00000440562

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 2023

The c.53C>G (p.P18R) alteration is located in exon 3 (coding exon 2) of the RELT gene. This alteration results from a C to G substitution at nucleotide position 53, causing the proline (P) at amino acid position 18 to be replaced by an arginine (R). 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

0.10

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.023

T;T;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.63

.;T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.1

M;.;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.81

N;N;N

REVEL

Benign

0.23

Sift

Uncertain

0.016

D;D;D

Sift4G

Benign

0.097

T;D;T

Polyphen

0.74

P;.;P

Vest4

0.32

MutPred

0.44

Gain of solvent accessibility (P = 0.0078);Gain of solvent accessibility (P = 0.0078);Gain of solvent accessibility (P = 0.0078);

MVP

0.52

MPC

0.11

ClinPred

0.18

GERP RS

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.084

gMVP

0.45

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