4-139016013-C-T

Variant names:

• chr4-139016013-C-T
• rs183350335
• NM_012118.4:c.32C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_012118.4(NOCT):​c.32C>T​(p.Ala11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,397,982 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (8 hom.)
• Consequence: NOCT NM_012118.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021380305).
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012118.4. 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
	NOCT	NM_012118.4	MANE Select	c.32C>T	p.Ala11Val	missense	Exon 1 of 3	NP_036250.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOCT	ENST00000280614.4	TSL:1 MANE Select	c.32C>T	p.Ala11Val	missense	Exon 1 of 3	ENSP00000280614.2	Q9UK39
	NOCT	ENST00000866809.1		c.32C>T	p.Ala11Val	missense	Exon 1 of 2	ENSP00000536868.1
	NOCT	ENST00000630479.1	TSL:5	n.32C>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000486546.1	Q8WTX0

Frequencies

GnomAD3 genomes AF: 0.000987 AC: 150 AN: 152006 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000779 AC: 40 AN: 51320 AF XY: 0.000818

Gnomad AFR exome AF: 0.00157

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: 0.00202

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00157 AC: 1956 AN: 1245868 Hom.: 8 Cov.: 31 AF XY: 0.00156 AC XY: 956 AN XY: 612708

African (AFR) AF: 0.000322 AC: 8 AN: 24852

American (AMR) AF: 0.000870 AC: 16 AN: 18390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19906

East Asian (EAS) AF: 0.00 AC: 0 AN: 26636

South Asian (SAS) AF: 0.0000162 AC: 1 AN: 61760

European-Finnish (FIN) AF: 0.0000979 AC: 3 AN: 30632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3576

European-Non Finnish (NFE) AF: 0.00187 AC: 1890 AN: 1009530

Other (OTH) AF: 0.000751 AC: 38 AN: 50586

GnomAD4 genome AF: 0.000986 AC: 150 AN: 152114 Hom.: 0 Cov.: 32 AF XY: 0.000766 AC XY: 57 AN XY: 74398

African (AFR) AF: 0.000385 AC: 16 AN: 41546

American (AMR) AF: 0.000393 AC: 6 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00188 AC: 128 AN: 67948

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000794 Hom.: 0

Bravo AF: 0.00105

ExAC AF: 0.000308 AC: 5

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	Uncertain	0.53
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.095	T
Eigen	Benign	0.092
Eigen_PC	Benign	0.043
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.2
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.064
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.023	D
Polyphen		0.98	D
Vest4		0.40
MVP		0.043
MPC		0.60
ClinPred		0.11	T
GERP RS		2.7
PromoterAI		-0.22	Neutral
Varity_R		0.17
gMVP		0.57
Mutation Taster		=78/22	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: rs183350335; hg19: chr4-139937167;