NOC2L p.Glu721Asp

Variant names:

• chr1-944781-C-A
• NM_015658.4:c.2163G>T
• NOC2L p.Glu721Asp

Your query was ambiguous. Multiple possible variants found:

• chr1-944781-C-A
• chr1-944781-C-G

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.2163G>T​(p.Glu721Asp) 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. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NOC2L NM_015658.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• 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]

SAMD11 (HGNC:28706): (sterile alpha motif domain containing 11) Predicted to enable several functions, including histone binding activity; protein domain specific binding activity; and protein self-association. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SAMD11 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Franklin by Genoox, G2P

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=0.11423451).

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.2163G>T	p.Glu721Asp	missense	Exon 19 of 19	NP_056473.3	Q9Y3T9
	SAMD11	NM_001385641.1	MANE Select	c.*628C>A		downstream_gene	N/A	NP_001372570.1	A0A087WU74
	SAMD11	NM_001385640.1		c.*628C>A		downstream_gene	N/A	NP_001372569.1	A0A087WX24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOC2L	ENST00000327044.7	TSL:1 MANE Select	c.2163G>T	p.Glu721Asp	missense	Exon 19 of 19	ENSP00000317992.6	Q9Y3T9
	NOC2L	ENST00000968819.1		c.2394G>T	p.Glu798Asp	missense	Exon 20 of 20	ENSP00000638878.1
	NOC2L	ENST00000934955.1		c.2280G>T	p.Glu760Asp	missense	Exon 19 of 19	ENSP00000605014.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.92	L
PhyloP100		1.0
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.076
Sift	Benign	0.33	T
Sift4G	Benign	0.38	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.056
gMVP		0.021
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-880161;