1-946213-C-A

Variant names:

• chr1-946213-C-A
• rs781123483
• NM_015658.4:c.1877G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015658.4(NOC2L):​c.1877G>T​(p.Arg626Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R626H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: NOC2L NM_015658.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.32
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.874

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015658.4. 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
	NOC2L	NM_015658.4	MANE Select	c.1877G>T	p.Arg626Leu	missense	Exon 16 of 19	NP_056473.3	Q9Y3T9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOC2L	ENST00000327044.7	TSL:1 MANE Select	c.1877G>T	p.Arg626Leu	missense	Exon 16 of 19	ENSP00000317992.6	Q9Y3T9
	NOC2L	ENST00000968819.1		c.2093G>T	p.Arg698Leu	missense	Exon 17 of 20	ENSP00000638878.1
	NOC2L	ENST00000934955.1		c.1979G>T	p.Arg660Leu	missense	Exon 16 of 19	ENSP00000605014.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250704 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.32	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.3
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.62		Loss of MoRF binding (P = 0.0326)
MVP		0.75
ClinPred		0.99	D
GERP RS		3.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
Varity_R		0.87
gMVP		0.61
Mutation Taster		=61/39	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: rs781123483; hg19: chr1-881593;