15-71810774-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014249.4(NR2E3):ā€‹c.31T>Gā€‹(p.Ser11Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000702 in 1,424,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000070 ( 0 hom. )

Consequence

NR2E3
NM_014249.4 missense

Scores

1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.37
Variant links:
Genes affected
NR2E3 (HGNC:7974): (nuclear receptor subfamily 2 group E member 3) This protein is part of a large family of nuclear receptor transcription factors involved in signaling pathways. Nuclear receptors have been shown to regulate pathways involved in embryonic development, as well as in maintenance of proper cell function in adults. Members of this family are characterized by discrete domains that function in DNA and ligand binding. This gene encodes a retinal nuclear receptor that is a ligand-dependent transcription factor. Defects in this gene are a cause of enhanced S cone syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.04880801).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NR2E3NM_014249.4 linkuse as main transcriptc.31T>G p.Ser11Ala missense_variant 1/8 ENST00000617575.5
NR2E3NM_016346.4 linkuse as main transcriptc.31T>G p.Ser11Ala missense_variant 1/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NR2E3ENST00000617575.5 linkuse as main transcriptc.31T>G p.Ser11Ala missense_variant 1/81 NM_014249.4 P1Q9Y5X4-1
NR2E3ENST00000621098.1 linkuse as main transcriptc.31T>G p.Ser11Ala missense_variant 1/71 Q9Y5X4-2
NR2E3ENST00000621736.4 linkuse as main transcriptc.-146-709T>G intron_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000702
AC:
10
AN:
1424606
Hom.:
0
Cov.:
31
AF XY:
0.00000709
AC XY:
5
AN XY:
705206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000914
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000468
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 04, 2023This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 11 of the NR2E3 protein (p.Ser11Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NR2E3-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NR2E3 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.063
BayesDel_addAF
Benign
-0.096
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
7.7
DANN
Benign
0.83
DEOGEN2
Benign
0.20
T;.
Eigen
Benign
-0.88
Eigen_PC
Benign
-0.83
FATHMM_MKL
Benign
0.025
N
LIST_S2
Benign
0.26
T;T
MetaRNN
Benign
0.049
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N;N
PrimateAI
Uncertain
0.62
T
Sift4G
Benign
0.30
T;T
Polyphen
0.0
B;.
Vest4
0.053
MutPred
0.38
Gain of helix (P = 6e-04);Gain of helix (P = 6e-04);
MVP
0.22
ClinPred
0.083
T
GERP RS
0.61
Varity_R
0.11
gMVP
0.34

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.

Other links and lift over

dbSNP: rs2054171751; hg19: chr15-72103114; API