GeneBe

chr19-54143150-C-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_014516.4(CNOT3):​c.57C>G​(p.Ser19Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S19S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CNOT3
NM_014516.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0510

Publications

0 publications found
Variant links:
Genes affected
CNOT3 (HGNC:7879): (CCR4-NOT transcription complex subunit 3) Involved in regulation of stem cell population maintenance. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Apr 2022]
CNOT3 Gene-Disease associations (from GenCC):
  • complex neurodevelopmental disorder
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • intellectual developmental disorder with speech delay, autism, and dysmorphic facies
    Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP7
Synonymous conserved (PhyloP=-0.051 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNOT3NM_014516.4 linkc.57C>G p.Ser19Ser synonymous_variant Exon 3 of 18 ENST00000221232.11 NP_055331.1 O75175A0A024R4R3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNOT3ENST00000221232.11 linkc.57C>G p.Ser19Ser synonymous_variant Exon 3 of 18 1 NM_014516.4 ENSP00000221232.5 O75175

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461698
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727134
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53288
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111952
Other (OTH)
AF:
0.00
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
CADD
Benign
11
DANN
Benign
0.71
PhyloP100
-0.051

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

Other links and lift over

dbSNP: rs138664639; hg19: chr19-54646886; API