NM_033334.4:c.1427G>A

Variant names:

• chr9-124522721-C-T
• rs61733760
• NM_033334.4:c.1427G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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. 14/21 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.59
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -16 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 VariationId is 790625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033334.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR6A1	NM_033334.4	MANE Select	c.1427G>A	p.Ser476Asn	missense	Exon 10 of 10	NP_201591.2
	NR6A1	NM_001410996.1		c.1424G>A	p.Ser475Asn	missense	Exon 10 of 10	NP_001397925.1	Q15406-4
	NR6A1	NM_001278546.2		c.1415G>A	p.Ser472Asn	missense	Exon 10 of 10	NP_001265475.1	F1DAM1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR6A1	ENST00000487099.7	TSL:1 MANE Select	c.1427G>A	p.Ser476Asn	missense	Exon 10 of 10	ENSP00000420267.1	Q15406-1
	NR6A1	ENST00000373584.7	TSL:1	c.1415G>A	p.Ser472Asn	missense	Exon 10 of 10	ENSP00000362686.3	Q15406-2
	NR6A1	ENST00000416460.6	TSL:1	c.1412G>A	p.Ser471Asn	missense	Exon 10 of 10	ENSP00000413701.2	Q15406-5

Frequencies

GnomAD3 genomes AF: 0.00434 AC: 661 AN: 152216 Hom.: 3 Cov.: 32

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

GnomAD2 exomes AF: 0.000980 AC: 202 AN: 206148 AF XY: 0.000697

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 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.: 1 Cov.: 30 AF XY: 0.000347 AC XY: 246 AN XY: 709422

African (AFR) AF: 0.0152 AC: 496 AN: 32676

American (AMR) AF: 0.000923 AC: 38 AN: 41160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25514

East Asian (EAS) AF: 0.00 AC: 0 AN: 37892

South Asian (SAS) AF: 0.0000246 AC: 2 AN: 81458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51318

Middle Eastern (MID) AF: 0.00131 AC: 7 AN: 5328

European-Non Finnish (NFE) AF: 0.0000201 AC: 22 AN: 1097206

Other (OTH) AF: 0.000878 AC: 52 AN: 59234

GnomAD4 genome AF: 0.00435 AC: 662 AN: 152334 Hom.: 3 Cov.: 32 AF XY: 0.00443 AC XY: 330 AN XY: 74498

African (AFR) AF: 0.0152 AC: 632 AN: 41576

American (AMR) AF: 0.00176 AC: 27 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00155 Hom.: 1

Bravo AF: 0.00493

ESP6500AA AF: 0.0125 AC: 55

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00124 AC: 150

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.062
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.81	L
PhyloP100		5.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.29
Sift	Benign	0.33	T
Sift4G	Benign	0.60	T
Polyphen		0.0030	B
Vest4		0.15
MVP		0.39
MPC		0.26
ClinPred		0.047	T
GERP RS		3.9
Varity_R		0.22
gMVP		0.42
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs61733760; hg19: chr9-127285000;