rs781377753

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-945611-C-A
• chr1-945611-C-G
• chr1-945611-C-T

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>T​(p.Ala654Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,216 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., 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=0.07227531).

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>T	p.Ala654Ser	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>T	p.Ala654Ser	missense	Exon 17 of 19	ENSP00000317992.6	Q9Y3T9
	NOC2L	ENST00000968819.1		c.2176G>T	p.Ala726Ser	missense	Exon 18 of 20	ENSP00000638878.1
	NOC2L	ENST00000934955.1		c.2062G>T	p.Ala688Ser	missense	Exon 17 of 19	ENSP00000605014.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.53
DEOGEN2	Benign	0.028	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.71
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.054
Sift	Benign	0.68	T
Sift4G	Benign	0.74	T
Polyphen		0.49	P
Vest4		0.075
MutPred		0.21		Gain of phosphorylation at A654 (P = 9e-04)
MVP		0.54
ClinPred		0.078	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.018
gMVP		0.095
Mutation Taster		=95/5	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;