1-946207-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015658.4(NOC2L):​c.1883G>A​(p.Arg628Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000248 in 1,613,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

NOC2L
NM_015658.4 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.04
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.057027042).
BS2
High AC in GnomAd4 at 38 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NOC2LNM_015658.4 linkc.1883G>A p.Arg628Gln missense_variant Exon 16 of 19 ENST00000327044.7 NP_056473.3 Q9Y3T9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NOC2LENST00000327044.7 linkc.1883G>A p.Arg628Gln missense_variant Exon 16 of 19 1 NM_015658.4 ENSP00000317992.6 Q9Y3T9
NOC2LENST00000477976.5 linkn.3330G>A non_coding_transcript_exon_variant Exon 14 of 17 5
NOC2LENST00000483767.5 linkn.739G>A non_coding_transcript_exon_variant Exon 2 of 5 2

Frequencies

GnomAD3 genomes
AF:
0.000250
AC:
38
AN:
152244
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00104
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.000200
AC:
50
AN:
250622
Hom.:
0
AF XY:
0.000221
AC XY:
30
AN XY:
135592
show subpopulations
Gnomad AFR exome
AF:
0.0000617
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00106
Gnomad NFE exome
AF:
0.000212
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000248
AC:
362
AN:
1460952
Hom.:
0
Cov.:
30
AF XY:
0.000227
AC XY:
165
AN XY:
726652
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000901
Gnomad4 NFE exome
AF:
0.000252
Gnomad4 OTH exome
AF:
0.000365
GnomAD4 genome
AF:
0.000249
AC:
38
AN:
152362
Hom.:
0
Cov.:
34
AF XY:
0.000309
AC XY:
23
AN XY:
74506
show subpopulations
Gnomad4 AFR
AF:
0.000240
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00104
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.000152
Hom.:
0
Bravo
AF:
0.000178
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000206
AC:
25
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 04, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1883G>A (p.R628Q) alteration is located in exon 16 (coding exon 16) of the NOC2L gene. This alteration results from a G to A substitution at nucleotide position 1883, causing the arginine (R) at amino acid position 628 to be replaced by a glutamine (Q). 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
0.11
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.38
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.029
T
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Uncertain
0.96
D
M_CAP
Uncertain
0.099
D
MetaRNN
Benign
0.057
T
MetaSVM
Benign
-0.37
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.085
Sift
Benign
0.15
T
Sift4G
Benign
0.33
T
Polyphen
0.99
D
Vest4
0.34
MVP
0.73
ClinPred
0.076
T
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.10
gMVP
0.081

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs150197742; hg19: chr1-881587; API