15-71810793-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_014249.4(NR2E3):c.50C>T(p.Ala17Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000362 in 1,576,504 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A17A) has been classified as Likely benign.
Frequency
Consequence
NM_014249.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR2E3 | NM_014249.4 | c.50C>T | p.Ala17Val | missense_variant | 1/8 | ENST00000617575.5 | |
NR2E3 | NM_016346.4 | c.50C>T | p.Ala17Val | missense_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR2E3 | ENST00000617575.5 | c.50C>T | p.Ala17Val | missense_variant | 1/8 | 1 | NM_014249.4 | P1 | |
NR2E3 | ENST00000621098.1 | c.50C>T | p.Ala17Val | missense_variant | 1/7 | 1 | |||
NR2E3 | ENST00000621736.4 | c.-146-690C>T | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000432 AC: 8AN: 185130Hom.: 0 AF XY: 0.0000199 AC XY: 2AN XY: 100254
GnomAD4 exome AF: 0.0000330 AC: 47AN: 1424188Hom.: 0 Cov.: 31 AF XY: 0.0000199 AC XY: 14AN XY: 705056
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152316Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74474
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 09, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 17 of the NR2E3 protein (p.Ala17Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 846003). 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. - |
Goldmann-Favre syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 13, 2020 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at