9-124538201-G-A

Variant names:

• chr9-124538201-G-A
• rs145792853
• NM_033334.4:c.715C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_033334.4(NR6A1):​c.715C>T​(p.Leu239Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NR6A1 NM_033334.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.883
• Publications: 2 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.883 with no splicing effect.

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.715C>T	p.Leu239Leu	synonymous	Exon 6 of 10	NP_201591.2
	NR6A1	NM_001410996.1		c.712C>T	p.Leu238Leu	synonymous	Exon 6 of 10	NP_001397925.1	Q15406-4
	NR6A1	NM_001278546.2		c.703C>T	p.Leu235Leu	synonymous	Exon 6 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.715C>T	p.Leu239Leu	synonymous	Exon 6 of 10	ENSP00000420267.1	Q15406-1
	NR6A1	ENST00000373584.7	TSL:1	c.703C>T	p.Leu235Leu	synonymous	Exon 6 of 10	ENSP00000362686.3	Q15406-2
	NR6A1	ENST00000416460.6	TSL:1	c.700C>T	p.Leu234Leu	synonymous	Exon 6 of 10	ENSP00000413701.2	Q15406-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251368 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.67
PhyloP100		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs145792853; hg19: chr9-127300480;