Genetic Variant NM_015658.4:c.2158G>T (chr1-944786-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015658.4(NOC2L):c.2158G>T(p.Ala720Ser) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A720T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NOC2L
NM_015658.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.597

Publications

0 publications found

Variant links:

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]

NOC2L links:

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, G2P, Franklin by Genoox

SAMD11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034546107).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOC2L	NM_015658.4	MANE Select	c.2158G>T	p.Ala720Ser	missense	Exon 19 of 19	NP_056473.3	Q9Y3T9
SAMD11	NM_001385641.1	MANE Select	c.*633C>A		downstream_gene	N/A	NP_001372570.1	A0A087WU74
SAMD11	NM_001385640.1		c.*633C>A		downstream_gene	N/A	NP_001372569.1	A0A087WX24

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOC2L	ENST00000327044.7	TSL:1 MANE Select	c.2158G>T	p.Ala720Ser	missense	Exon 19 of 19	ENSP00000317992.6	Q9Y3T9
NOC2L	ENST00000968819.1		c.2389G>T	p.Ala797Ser	missense	Exon 20 of 20	ENSP00000638878.1
NOC2L	ENST00000934955.1		c.2275G>T	p.Ala759Ser	missense	Exon 19 of 19	ENSP00000605014.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1438206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715624

African (AFR)

AF:

0.00

AC:

AN:

32678

American (AMR)

AF:

0.00

AC:

AN:

42258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25754

East Asian (EAS)

AF:

0.00

AC:

AN:

39474

South Asian (SAS)

AF:

0.00

AC:

AN:

85022

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104722

Other (OTH)

AF:

0.00

AC:

AN:

59514

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.16

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.016

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.64

M_CAP

Benign

0.0069

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

-0.60

PrimateAI

Benign

0.34

PROVEAN

Benign

0.48

REVEL

Benign

0.040

Sift

Benign

0.50

Sift4G

Benign

0.74

Polyphen

0.19

Vest4

0.079

MutPred

0.098

Gain of phosphorylation at A720 (P = 0.0033)

MVP

0.26

ClinPred

0.16

GERP RS

-7.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.030

gMVP

0.034

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over