chr1-944781-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015658.4(NOC2L):​c.2163G>C​(p.Glu721Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000815 in 1,595,932 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

NOC2L
NM_015658.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.00
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09022161).
BS2
High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NOC2LNM_015658.4 linkc.2163G>C p.Glu721Asp missense_variant Exon 19 of 19 ENST00000327044.7 NP_056473.3 Q9Y3T9
SAMD11NM_001385641.1 linkc.*628C>G downstream_gene_variant ENST00000616016.5 NP_001372570.1
SAMD11NM_001385640.1 linkc.*628C>G downstream_gene_variant NP_001372569.1
SAMD11NM_152486.4 linkc.*628C>G downstream_gene_variant NP_689699.3 Q96NU1-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NOC2LENST00000327044.7 linkc.2163G>C p.Glu721Asp missense_variant Exon 19 of 19 1 NM_015658.4 ENSP00000317992.6 Q9Y3T9
SAMD11ENST00000616016.5 linkc.*628C>G downstream_gene_variant 5 NM_001385641.1 ENSP00000478421.2 A0A087WU74

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152238
Hom.:
0
Cov.:
33
show subpopulations
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:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000174
AC:
4
AN:
229422
Hom.:
0
AF XY:
0.00000787
AC XY:
1
AN XY:
127026
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000140
Gnomad NFE exome
AF:
0.0000188
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000762
AC:
11
AN:
1443694
Hom.:
0
Cov.:
29
AF XY:
0.00000974
AC XY:
7
AN XY:
718492
show subpopulations
Gnomad4 AFR exome
AF:
0.0000303
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000463
Gnomad4 NFE exome
AF:
0.00000542
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152238
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000828
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2163G>C (p.E721D) alteration is located in exon 19 (coding exon 19) of the NOC2L gene. This alteration results from a G to C substitution at nucleotide position 2163, causing the glutamic acid (E) at amino acid position 721 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
12
DANN
Benign
0.96
DEOGEN2
Benign
0.031
T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.0078
T
MetaRNN
Benign
0.090
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.92
L
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-0.73
N
REVEL
Benign
0.076
Sift
Benign
0.33
T
Sift4G
Benign
0.38
T
Polyphen
0.65
P
Vest4
0.21
MutPred
0.091
Loss of solvent accessibility (P = 0.0721);
MVP
0.47
ClinPred
0.053
T
GERP RS
2.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
Varity_R
0.056
gMVP
0.021

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.

Other links and lift over

dbSNP: rs756794372; hg19: chr1-880161; API