Genetic Variant NM_033334.4:c.1095G>C (chr9-124526885-C-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_033334.4(NR6A1):c.1095G>C(p.Gly365Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,613,994 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000093 ( 0 hom. )

Consequence

NR6A1
NM_033334.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0630

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:

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ACMG classification

Classification made for transcript

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=-0.45).

BP6

Variant 9-124526885-C-G is Benign according to our data. Variant chr9-124526885-C-G is described in ClinVar as [Benign]. Clinvar id is 740256.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.063 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR6A1	NM_033334.4 link	c.1095G>C	p.Gly365Gly	synonymous_variant	Exon 8 of 10	ENST00000487099.7	NP_201591.2	Q15406-1F1D8S0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NR6A1	ENST00000487099.7 link	c.1095G>C	p.Gly365Gly	synonymous_variant	Exon 8 of 10	1	NM_033334.4	ENSP00000420267.1	Q15406-1
NR6A1	ENST00000373584.7 link	c.1083G>C	p.Gly361Gly	synonymous_variant	Exon 8 of 10	1		ENSP00000362686.3	Q15406-2
NR6A1	ENST00000416460.6 link	c.1080G>C	p.Gly360Gly	synonymous_variant	Exon 8 of 10	1		ENSP00000413701.2	Q15406-5
NR6A1	ENST00000344523.8 link	c.1092G>C	p.Gly364Gly	synonymous_variant	Exon 8 of 10	5		ENSP00000341135.4	Q15406-4

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

164

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000956

GnomAD3 exomes

AF:

0.000294

AC:

AN:

251384

Hom.:

AF XY:

0.000199

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00431

Gnomad AMR exome

AF:

0.0000578

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:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000930

AC:

136

AN:

1461684

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.00352

Gnomad4 AMR exome

AF:

0.0000894

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:

0.000182

GnomAD4 genome

AF:

0.00107

AC:

163

AN:

152310

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00383

Gnomad4 AMR

AF:

0.000131

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:

0.000946

Alfa

AF:

0.000225

Hom.:

Bravo

AF:

0.00112

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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

-0.45

CADD

Benign

6.8

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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