NM_014249.4:c.50C>A

Variant names:

• chr15-71810793-C-A
• NM_014249.4:c.50C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014249.4(NR2E3):​c.50C>A​(p.Ala17Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NR2E3 NM_014249.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0561257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR2E3	NM_014249.4	c.50C>A	p.Ala17Glu	missense_variant	Exon 1 of 8	ENST00000617575.5	NP_055064.1
NR2E3	NM_016346.4	c.50C>A	p.Ala17Glu	missense_variant	Exon 1 of 7		NP_057430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR2E3	ENST00000617575.5	c.50C>A	p.Ala17Glu	missense_variant	Exon 1 of 8	1	NM_014249.4	ENSP00000482504.1
NR2E3	ENST00000621098.1	c.50C>A	p.Ala17Glu	missense_variant	Exon 1 of 7	1		ENSP00000479962.1
NR2E3	ENST00000621736.4	c.-146-690C>A		intron_variant	Intron 3 of 9	2		ENSP00000479254.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1424188 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 705056

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	0.48
DANN	Benign	0.87
DEOGEN2	Benign	0.17	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.42	T;T
MetaRNN	Benign	0.056	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	0.52	T;T
Polyphen		0.18	B;.
Vest4		0.10
MutPred		0.29		Gain of solvent accessibility (P = 0.0338);Gain of solvent accessibility (P = 0.0338);
MVP		0.081
ClinPred		0.19	T
GERP RS		-1.0
Varity_R		0.066
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-72103133;