4-139045332-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012118.4(NOCT):​c.1154C>G​(p.Ala385Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NOCT
NM_012118.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.87
Variant links:
Genes affected
NOCT (HGNC:14254): (nocturnin) The protein encoded by this gene is highly similar to Nocturnin, a gene identified as a circadian clock regulated gene in Xenopus laevis. This protein and Nocturnin protein share similarity with the C-terminal domain of a yeast transcription factor, carbon catabolite repression 4 (CCR4). The mRNA abundance of a similar gene in mouse has been shown to exhibit circadian rhythmicity, which suggests a role for this protein in clock function or as a circadian clock effector. [provided by RefSeq, Jul 2008]
ELF2 (HGNC:3317): (E74 like ETS transcription factor 2) Enables DNA-binding transcription factor activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription, DNA-templated; positive regulation of transcription, DNA-templated; and regulation of transcription by RNA polymerase II. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3120922).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NOCTNM_012118.4 linkc.1154C>G p.Ala385Gly missense_variant Exon 3 of 3 ENST00000280614.4 NP_036250.2 Q9UK39

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NOCTENST00000280614.4 linkc.1154C>G p.Ala385Gly missense_variant Exon 3 of 3 1 NM_012118.4 ENSP00000280614.2 Q9UK39
ELF2ENST00000515489.1 linkn.272+14992G>C intron_variant Intron 1 of 1 2
NOCTENST00000630479.1 linkn.*505-230C>G intron_variant Intron 2 of 2 5 ENSP00000486546.1 Q8WTX0
NOCTENST00000515616.1 linkn.*227C>G downstream_gene_variant 1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
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
Feb 25, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1154C>G (p.A385G) alteration is located in exon 3 (coding exon 3) of the NOCT gene. This alteration results from a C to G substitution at nucleotide position 1154, causing the alanine (A) at amino acid position 385 to be replaced by a glycine (G). 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
Benign
0.13
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
20
DANN
Benign
0.68
DEOGEN2
Benign
0.18
T
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.34
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.85
L
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.093
Sift
Benign
0.45
T
Sift4G
Benign
0.35
T
Polyphen
0.022
B
Vest4
0.49
MutPred
0.54
Loss of stability (P = 0.0563);
MVP
0.11
MPC
0.32
ClinPred
0.71
D
GERP RS
4.8
Varity_R
0.36
gMVP
0.54

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: chr4-139966486; API