NM_014249.4:c.39G>A

Variant names:

• chr15-71810782-G-A
• rs1392532455
• NM_014249.4:c.39G>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_014249.4(NR2E3):​c.39G>A​(p.Val13Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,424,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NR2E3 NM_014249.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.854

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 15-71810782-G-A is Benign according to our data. Variant chr15-71810782-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1090447.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.854 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR2E3	NM_014249.4	c.39G>A	p.Val13Val	synonymous_variant	Exon 1 of 8	ENST00000617575.5	NP_055064.1
NR2E3	NM_016346.4	c.39G>A	p.Val13Val	synonymous_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.39G>A	p.Val13Val	synonymous_variant	Exon 1 of 8	1	NM_014249.4	ENSP00000482504.1
NR2E3	ENST00000621098.1	c.39G>A	p.Val13Val	synonymous_variant	Exon 1 of 7	1		ENSP00000479962.1
NR2E3	ENST00000621736.4	c.-146-701G>A		intron_variant	Intron 3 of 9	2		ENSP00000479254.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1424028 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 704928

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: 0.00000274

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 02, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	8.4
DANN	Benign	0.82

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

Other links and lift over

dbSNP: rs1392532455; hg19: chr15-72103122;