6-108176636-C-G

Position:

• chr6-108176636-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003269.5(NR2E1):​c.393C>G​(p.Phe131Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NR2E1 NM_003269.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61

Genes affected

NR2E1 (HGNC:7973): (nuclear receptor subfamily 2 group E member 1) The protein encoded by this gene is an orphan receptor involved in retinal development. The encoded protein also regulates adult neural stem cell proliferation and may be involved in control of aggressive behavior. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

NR2E1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR2E1	NM_003269.5	c.393C>G	p.Phe131Leu	missense_variant	4/9	ENST00000368986.9	NP_003260.1
NR2E1	NM_001286102.1	c.504C>G	p.Phe168Leu	missense_variant	4/9		NP_001273031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR2E1	ENST00000368986.9	c.393C>G	p.Phe131Leu	missense_variant	4/9	1	NM_003269.5	ENSP00000357982.5
NR2E1	ENST00000368983.3	c.504C>G	p.Phe168Leu	missense_variant	4/9	2		ENSP00000357979.3
NR2E1	ENST00000484978.1	n.356C>G		non_coding_transcript_exon_variant	2/3	5
NR2E1	ENST00000426403.1	c.*10C>G		downstream_gene_variant		4		ENSP00000416908.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2022

The c.393C>G (p.F131L) alteration is located in exon 4 (coding exon 4) of the NR2E1 gene. This alteration results from a C to G substitution at nucleotide position 393, causing the phenylalanine (F) at amino acid position 131 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.0015	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-0.092
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.50	N;N
REVEL	Benign	0.097
Sift	Benign	0.70	T;T
Sift4G	Benign	0.75	T;T
Polyphen		0.024	B;.
Vest4		0.82
MutPred		0.31		Gain of disorder (P = 0.139);.;
MVP		0.57
MPC		1.0
ClinPred		0.70	D
GERP RS		5.8
Varity_R		0.18
gMVP		0.85

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: chr6-108497840;