Variant 6-108176607-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003269.5(NR2E1):c.364T>C(p.Ser122Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,612,270 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000093 ( 0 hom. )

Consequence

NR2E1
NM_003269.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.91

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:

NR2E1 (HGNC:):

NR2E1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012334615).

BS2

High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR2E1	NM_003269.5 linkuse as main transcript	c.364T>C	p.Ser122Pro	missense_variant	4/9	ENST00000368986.9	NP_003260.1	Q9Y466-1B6ZGT9
NR2E1	NM_001286102.1 linkuse as main transcript	c.475T>C	p.Ser159Pro	missense_variant	4/9		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.364T>C	p.Ser122Pro	missense_variant	4/9	1	NM_003269.5	ENSP00000357982.5	Q9Y466-1
NR2E1	ENST00000368983.3 linkuse as main transcript	c.475T>C	p.Ser159Pro	missense_variant	4/9	2		ENSP00000357979.3	Q9Y466-2
NR2E1	ENST00000426403.1 linkuse as main transcript	c.118T>C	p.Ser40Pro	missense_variant	4/4	4		ENSP00000416908.1	A6PVF6
NR2E1	ENST00000484978.1 linkuse as main transcript	n.327T>C		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000147

AC:

AN:

244620

Hom.:

AF XY:

0.000172

AC XY:

AN XY:

133804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00232

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000548

Gnomad OTH exome

AF:

0.000833

GnomAD4 exome

AF:

0.0000932

AC:

136

AN:

1459962

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

726332

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00234

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000171

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000190

Hom.:

Bravo

AF:

0.000166

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

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

Feb 22, 2023

The c.364T>C (p.S122P) alteration is located in exon 4 (coding exon 4) of the NR2E1 gene. This alteration results from a T to C substitution at nucleotide position 364, causing the serine (S) at amino acid position 122 to be replaced by a proline (P). 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

0.063

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;.;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.60

N;.;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.77

N;N;N

REVEL

Benign

0.050

Sift

Benign

0.36

T;T;D

Sift4G

Benign

0.40

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.19

MVP

0.40

MPC

1.5

ClinPred

0.019

GERP RS

4.6

Varity_R

0.20

gMVP

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

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