Genetic Variant NOC2L:p.Glu708Asp (chr1-945076-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015658.4(NOC2L):c.2124G>C(p.Glu708Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

NOC2L
NM_015658.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.38

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030776203).

BP6

Variant 1-945076-C-G is Benign according to our data. Variant chr1-945076-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3200948.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOC2L	NM_015658.4 link	c.2124G>C	p.Glu708Asp	missense_variant	Exon 18 of 19	ENST00000327044.7	NP_056473.3	Q9Y3T9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOC2L	ENST00000327044.7 link	c.2124G>C	p.Glu708Asp	missense_variant	Exon 18 of 19	1	NM_015658.4	ENSP00000317992.6	Q9Y3T9
NOC2L	ENST00000477976.5 link	n.3571G>C		non_coding_transcript_exon_variant	Exon 16 of 17	5
NOC2L	ENST00000483767.5 link	n.980G>C		non_coding_transcript_exon_variant	Exon 4 of 5	2
NOC2L	ENST00000496938.1 link	n.*243G>C		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000684

AC:

AN:

248430

Hom.:

AF XY:

0.0000594

AC XY:

AN XY:

134608

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000308

AC:

AN:

1461676

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.0000342

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 19, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0020

DANN

Benign

0.53

DEOGEN2

Benign

0.026

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.26

M_CAP

Benign

0.0078

MetaRNN

Benign

0.031

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.49

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.49

REVEL

Benign

0.015

Sift

Benign

0.35

Sift4G

Benign

0.25

Polyphen

0.0010

Vest4

0.17

MutPred

0.13

Loss of solvent accessibility (P = 0.239);

MVP

0.22

ClinPred

0.037

GERP RS

-3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.023

gMVP

0.017

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over