1-945611-C-G

Variant names:

• chr1-945611-C-G
• rs781377753
• NM_015658.4:c.1960G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015658.4(NOC2L):​c.1960G>C​(p.Ala654Pro) 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. 17/22 in silico tools predict a benign 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. A654T) 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: 0.714
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.113000125).

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.1960G>C	p.Ala654Pro	missense	Exon 17 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.1960G>C	p.Ala654Pro	missense	Exon 17 of 19	ENSP00000317992.6	Q9Y3T9
	NOC2L	ENST00000968819.1		c.2176G>C	p.Ala726Pro	missense	Exon 18 of 20	ENSP00000638878.1
	NOC2L	ENST00000934955.1		c.2062G>C	p.Ala688Pro	missense	Exon 17 of 19	ENSP00000605014.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.68
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.71
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.079
Sift	Benign	0.25	T
Sift4G	Benign	0.30	T
Polyphen		0.82	P
Vest4		0.099
MutPred		0.20		Gain of glycosylation at A654 (P = 0.0202)
MVP		0.63
ClinPred		0.19	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.055
gMVP		0.15
Mutation Taster		=90/10	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: rs781377753; hg19: chr1-880991;