NM_015658.4:c.1984A>G

Variant names:

• chr1-945587-T-C
• NM_015658.4:c.1984A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015658.4(NOC2L):​c.1984A>G​(p.Lys662Glu) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NOC2L NM_015658.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57

Genes affected

NOC2L (HGNC:24517): (NOC2 like nucleolar associated transcriptional repressor) Histone modification by histone acetyltransferases (HAT) and histone deacetylases (HDAC) can control major aspects of transcriptional regulation. NOC2L represents a novel HDAC-independent inhibitor of histone acetyltransferase (INHAT) (Hublitz et al., 2005 [PubMed 16322561]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026441872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOC2L	NM_015658.4	c.1984A>G	p.Lys662Glu	missense_variant	Exon 17 of 19	ENST00000327044.7	NP_056473.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOC2L	ENST00000327044.7	c.1984A>G	p.Lys662Glu	missense_variant	Exon 17 of 19	1	NM_015658.4	ENSP00000317992.6
NOC2L	ENST00000477976.5	n.3431A>G		non_coding_transcript_exon_variant	Exon 15 of 17	5
NOC2L	ENST00000483767.5	n.840A>G		non_coding_transcript_exon_variant	Exon 3 of 5	2
NOC2L	ENST00000496938.1	n.-25A>G		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1984A>G (p.K662E) alteration is located in exon 17 (coding exon 17) of the NOC2L gene. This alteration results from a A to G substitution at nucleotide position 1984, causing the lysine (K) at amino acid position 662 to be replaced by a glutamic acid (E). 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	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.088
Sift	Benign	0.73	T
Sift4G	Benign	0.89	T
Polyphen		0.016	B
Vest4		0.10
MutPred		0.18		Loss of ubiquitination at K662 (P = 0.0043);
MVP		0.45
ClinPred		0.034	T
GERP RS		1.8
Varity_R		0.029
gMVP		0.18

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: chr1-880967;