Variant chr6-108171601-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003269.5(NR2E1):c.169C>G(p.Gln57Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NR2E1
NM_003269.5 missense, splice_region

Scores

Splicing: ADA: 0.6841

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.31

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3705387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR2E1	NM_003269.5 linkuse as main transcript	c.169C>G	p.Gln57Glu	missense_variant, splice_region_variant	2/9	ENST00000368986.9	NP_003260.1	Q9Y466-1B6ZGT9
NR2E1	NM_001286102.1 linkuse as main transcript	c.280C>G	p.Gln94Glu	missense_variant, splice_region_variant	2/9		NP_001273031.1	Q9Y466-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NR2E1	ENST00000368986.9 linkuse as main transcript	c.169C>G	p.Gln57Glu	missense_variant, splice_region_variant	2/9	1	NM_003269.5	ENSP00000357982.5	Q9Y466-1
NR2E1	ENST00000368983.3 linkuse as main transcript	c.280C>G	p.Gln94Glu	missense_variant, splice_region_variant	2/9	2		ENSP00000357979.3	Q9Y466-2
NR2E1	ENST00000426403.1 linkuse as main transcript	c.-78C>G		splice_region_variant	2/4	4		ENSP00000416908.1	A6PVF6
NR2E1	ENST00000426403.1 linkuse as main transcript	c.-78C>G		5_prime_UTR_variant	2/4	4		ENSP00000416908.1	A6PVF6

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461756

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727166

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2023

The c.169C>G (p.Q57E) alteration is located in exon 2 (coding exon 2) of the NR2E1 gene. This alteration results from a C to G substitution at nucleotide position 169, causing the glutamine (Q) at amino acid position 57 to be replaced by a glutamic acid (E). 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

Benign

0.13

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.40

T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

0.067

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.37

T;T

MetaSVM

Uncertain

-0.20

MutationAssessor

Benign

0.050

N;.

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.0

N;N

REVEL

Uncertain

0.45

Sift

Benign

0.38

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.010

B;.

Vest4

0.60

MutPred

0.39

Gain of ubiquitination at K53 (P = 0.0381);.;

MVP

0.74

MPC

1.9

ClinPred

0.80

GERP RS

5.2

Varity_R

0.26

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.68

dbscSNV1_RF

Benign

0.41

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over