Variant 9-124522721-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_033334.4(NR6A1):c.1427G>A(p.Ser476Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000807 in 1,584,120 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 1 hom. )

Consequence

NR6A1
NM_033334.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.59

Variant links:

Genes affected

NR6A1 (HGNC:7985): (nuclear receptor subfamily 6 group A member 1) This gene encodes an orphan nuclear receptor which is a member of the nuclear hormone receptor family. Its expression pattern suggests that it may be involved in neurogenesis and germ cell development. The protein can homodimerize and bind DNA, but in vivo targets have not been identified. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jun 2013]

NR6A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00385046).

BP6

Variant 9-124522721-C-T is Benign according to our data. Variant chr9-124522721-C-T is described in ClinVar as [Benign]. Clinvar id is 790625.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR6A1	NM_033334.4 linkuse as main transcript	c.1427G>A	p.Ser476Asn	missense_variant	10/10	ENST00000487099.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR6A1	ENST00000487099.7 linkuse as main transcript	c.1427G>A	p.Ser476Asn	missense_variant	10/10	1	NM_033334.4	P4	Q15406-1
NR6A1	ENST00000373584.7 linkuse as main transcript	c.1415G>A	p.Ser472Asn	missense_variant	10/10	1		A1	Q15406-2
NR6A1	ENST00000416460.6 linkuse as main transcript	c.1412G>A	p.Ser471Asn	missense_variant	10/10	1		A1	Q15406-5
NR6A1	ENST00000344523.8 linkuse as main transcript	c.1424G>A	p.Ser475Asn	missense_variant	10/10	5		A1	Q15406-4

Frequencies

GnomAD3 genomes

AF:

0.00434

AC:

661

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

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:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000980

AC:

202

AN:

206148

Hom.:

AF XY:

0.000697

AC XY:

AN XY:

110400

show subpopulations

Gnomad AFR exome

AF:

0.0140

Gnomad AMR exome

AF:

0.000787

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000111

Gnomad OTH exome

AF:

0.000564

GnomAD4 exome

AF:

0.000431

AC:

617

AN:

1431786

Hom.:

Cov.:

AF XY:

0.000347

AC XY:

246

AN XY:

709422

show subpopulations

Gnomad4 AFR exome

AF:

0.0152

Gnomad4 AMR exome

AF:

0.000923

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000246

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000201

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.00435

AC:

662

AN:

152334

Hom.:

Cov.:

AF XY:

0.00443

AC XY:

330

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0152

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000660

Hom.:

Bravo

AF:

0.00493

ESP6500AA

AF:

0.0125

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00124

AC:

150

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.14

T;.;.;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.062

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.73

T;T;T;T

MetaRNN

Benign

0.0039

T;T;T;T

MetaSVM

Benign

-0.51

MutationAssessor

Benign

0.81

L;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.20

N;N;N;N

REVEL

Benign

0.29

Sift

Benign

0.33

T;T;T;T

Sift4G

Benign

0.60

T;T;T;T

Polyphen

0.0030

B;.;B;.

Vest4

0.15

MVP

0.39

MPC

0.26

ClinPred

0.047

GERP RS

3.9

Varity_R

0.22

gMVP

0.42

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