9-124522721-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033334.4(NR6A1):​c.1427G>C​(p.Ser476Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S476N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NR6A1 NM_033334.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20524433).

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>C	p.Ser476Thr	missense	Exon 10 of 10	NP_201591.2
	NR6A1	NM_001410996.1		c.1424G>C	p.Ser475Thr	missense	Exon 10 of 10	NP_001397925.1	Q15406-4
	NR6A1	NM_001278546.2		c.1415G>C	p.Ser472Thr	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>C	p.Ser476Thr	missense	Exon 10 of 10	ENSP00000420267.1	Q15406-1
	NR6A1	ENST00000373584.7	TSL:1	c.1415G>C	p.Ser472Thr	missense	Exon 10 of 10	ENSP00000362686.3	Q15406-2
	NR6A1	ENST00000416460.6	TSL:1	c.1412G>C	p.Ser471Thr	missense	Exon 10 of 10	ENSP00000413701.2	Q15406-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.040
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	0.10	D
MutationAssessor	Benign	0.81	L
PhyloP100		5.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.51	N
REVEL	Uncertain	0.40
Sift	Benign	0.068	T
Sift4G	Benign	0.42	T
Polyphen		0.46	P
Vest4		0.28
MutPred		0.18		Gain of methylation at K479 (P = 0.0778)
MVP		0.60
MPC		0.26
ClinPred		0.67	D
GERP RS		3.9
Varity_R		0.20
gMVP		0.39
Mutation Taster		=88/12	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;