3-23959738-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005126.5(NR1D2):​c.440C>T​(p.Ser147Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,606 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NR1D2
NM_005126.5 missense

Scores

5
11
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.89
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NR1D2NM_005126.5 linkc.440C>T p.Ser147Phe missense_variant Exon 4 of 8 ENST00000312521.9 NP_005117.3 Q14995F1D8P2
NR1D2NM_001145425.2 linkc.215C>T p.Ser72Phe missense_variant Exon 4 of 8 NP_001138897.1 B4DXD3
NR1D2XM_006713451.4 linkc.440C>T p.Ser147Phe missense_variant Exon 4 of 7 XP_006713514.1
NR1D2NR_110524.2 linkn.733C>T non_coding_transcript_exon_variant Exon 4 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NR1D2ENST00000312521.9 linkc.440C>T p.Ser147Phe missense_variant Exon 4 of 8 1 NM_005126.5 ENSP00000310006.3 Q14995
NR1D2ENST00000383773.8 linkn.440C>T non_coding_transcript_exon_variant Exon 4 of 9 1 ENSP00000373283.3 Q6NSM0
NR1D2ENST00000468700.1 linkn.335C>T non_coding_transcript_exon_variant Exon 3 of 4 3
NR1D2ENST00000492552.5 linkn.557C>T non_coding_transcript_exon_variant Exon 4 of 8 2 ENSP00000520893.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461606
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727104
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 18, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.440C>T (p.S147F) alteration is located in exon 4 (coding exon 4) of the NR1D2 gene. This alteration results from a C to T substitution at nucleotide position 440, causing the serine (S) at amino acid position 147 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.34
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
32
DANN
Uncertain
1.0
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.96
D
M_CAP
Pathogenic
0.42
D
MetaRNN
Uncertain
0.59
D
MetaSVM
Pathogenic
1.0
D
PrimateAI
Pathogenic
0.83
D
PROVEAN
Uncertain
-2.4
N
REVEL
Pathogenic
0.70
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.026
D
Vest4
0.51
MutPred
0.40
Loss of disorder (P = 0.0325);
MVP
0.67
MPC
0.83
ClinPred
0.96
D
GERP RS
5.0
gMVP
0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-24001229; API