chr3-23962115-C-G

Variant names:

• chr3-23962115-C-G
• NM_005126.5:c.656C>G

Variant summary

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

The NM_005126.5(NR1D2):​c.656C>G​(p.Thr219Arg) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NR1D2 NM_005126.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.80
• Publications: 0 publications found

Genes affected

NR1D2 (HGNC:7963): (nuclear receptor subfamily 1 group D member 2) This gene encodes a member of the nuclear hormone receptor family, specifically the NR1 subfamily of receptors. The encoded protein functions as a transcriptional repressor and may play a role in circadian rhythms and carbohydrate and lipid metabolism. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

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=0.11170003).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005126.5. 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
	NR1D2	NM_005126.5	MANE Select	c.656C>G	p.Thr219Arg	missense	Exon 5 of 8	NP_005117.3
	NR1D2	NM_001145425.2		c.431C>G	p.Thr144Arg	missense	Exon 5 of 8	NP_001138897.1	B4DXD3
	NR1D2	NR_110524.2		n.949C>G		non_coding_transcript_exon	Exon 5 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1D2	ENST00000312521.9	TSL:1 MANE Select	c.656C>G	p.Thr219Arg	missense	Exon 5 of 8	ENSP00000310006.3	Q14995
	NR1D2	ENST00000383773.8	TSL:1	n.656C>G		non_coding_transcript_exon	Exon 5 of 9	ENSP00000373283.3	Q6NSM0
	NR1D2	ENST00000947380.1		c.656C>G	p.Thr219Arg	missense	Exon 5 of 7	ENSP00000617439.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	16
DANN	Uncertain	0.98
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.56	T
PhyloP100		2.8
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.88	N
REVEL	Uncertain	0.31
Sift	Benign	0.051	T
Sift4G	Benign	0.46	T
Vest4		0.19
MutPred		0.15		Loss of glycosylation at T219 (P = 0.0764)
MVP		0.65
MPC		0.25
ClinPred		0.20	T
GERP RS		5.1
gMVP		0.36
Mutation Taster		=87/13	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

hg19: chr3-24003606;