chr15-71810745-T-G
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Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1
The NM_014249.4(NR2E3):āc.2T>Gā(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000115 in 1,566,682 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.000012 ( 0 hom. )
Consequence
NR2E3
NM_014249.4 start_lost
NM_014249.4 start_lost
Scores
3
8
Clinical Significance
Conservation
PhyloP100: -0.0950
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
Start lost variant, no new inframe start found.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR2E3 | NM_014249.4 | c.2T>G | p.Met1? | start_lost | 1/8 | ENST00000617575.5 | |
NR2E3 | NM_016346.4 | c.2T>G | p.Met1? | start_lost | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR2E3 | ENST00000617575.5 | c.2T>G | p.Met1? | start_lost | 1/8 | 1 | NM_014249.4 | P1 | |
NR2E3 | ENST00000621098.1 | c.2T>G | p.Met1? | start_lost | 1/7 | 1 | |||
NR2E3 | ENST00000621736.4 | c.-146-738T>G | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152144Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000569 AC: 1AN: 175702Hom.: 0 AF XY: 0.0000106 AC XY: 1AN XY: 94232
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GnomAD4 exome AF: 0.0000120 AC: 17AN: 1414538Hom.: 0 Cov.: 31 AF XY: 0.0000143 AC XY: 10AN XY: 699244
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74306
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Enhanced S-cone syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 25, 2020 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 28, 2022 | This sequence change affects the initiator methionine of the NR2E3 mRNA. The next in-frame methionine is located at codon 9. This variant is present in population databases (no rsID available, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with NR2E3-related conditions. ClinVar contains an entry for this variant (Variation ID: 942544). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
Sift4G
Uncertain
D;D
Polyphen
B;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0118);Gain of MoRF binding (P = 0.0118);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at