Variant 11-73390894-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate

The NM_152222.2(RELT):c.260A>T(p.Asp87Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Consequence

RELT
NM_152222.2 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 5.20

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:

RELT (HGNC:):

RELT links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.91

PP5

Variant 11-73390894-A-T is Pathogenic according to our data. Variant chr11-73390894-A-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2573131.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELT	NM_152222.2 linkuse as main transcript	c.260A>T	p.Asp87Val	missense_variant	4/11	ENST00000064780.7	NP_689408.1	Q969Z4A0A024R5N3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RELT	ENST00000064780.7 linkuse as main transcript	c.260A>T	p.Asp87Val	missense_variant	4/11	1	NM_152222.2	ENSP00000064780.2	Q969Z4
RELT	ENST00000393580.2 linkuse as main transcript	c.260A>T	p.Asp87Val	missense_variant	4/11	1		ENSP00000377207.2	Q969Z4
RELT	ENST00000545687.5 linkuse as main transcript	c.260A>T	p.Asp87Val	missense_variant	6/7	4		ENSP00000439352.1	F5H2T5
RELT	ENST00000544075.5 linkuse as main transcript	n.260A>T		non_coding_transcript_exon_variant	4/6	3		ENSP00000440562.1	F5GYS9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250342

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135408

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Amelogenesis imperfecta

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Department Of Pediatric Dentistry, Peking University School And Hospital Of Stomatology

May 20, 2023

Homozygous mutations in RELT have been reported to cause autosomal recessive AI. Multiple missense mutations have been reported to be associated with AI. The variant cosegregation with the disease in this family. The RELT variant (c.260A>T) is documented in the dbSNP database (rs771045558) with a minor allele frequency (MAF) count of 1/120740. This missense variant was predicted to be damaging, diseasing causing in SIFT (0.0, Deleterious), Polyphen2_HDIV (1.0, Probably damaging), MutationTaster (1, Disease-causing) and CADD (score: 24.6). These nucleotide change in RELT were absent in 144 ethnically matched normal controls. Amino-acid alignment analysis revealed that the affected residues were highly conserved among different species. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

T;D;T

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

.;D;D

M_CAP

Pathogenic

0.44

MetaRNN

Pathogenic

0.91

D;D;D

MetaSVM

Pathogenic

0.80

MutationAssessor

Pathogenic

3.4

M;.;M

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.5

D;D;D

REVEL

Pathogenic

0.80

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.91

MutPred

0.68

Loss of solvent accessibility (P = 0.0219);Loss of solvent accessibility (P = 0.0219);Loss of solvent accessibility (P = 0.0219);

MVP

0.86

MPC

0.64

ClinPred

0.97

GERP RS

5.3

Varity_R

0.40

gMVP

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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