16-15888570-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_144600.4(CEP20):​c.16G>C​(p.Glu6Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E6G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CEP20
NM_144600.4 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

Publications

0 publications found
Variant links:
Genes affected
CEP20 (HGNC:26435): (centrosomal protein 20) Enables identical protein binding activity. Involved in cilium assembly. Located in centriolar satellite and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CEP20NM_144600.4 linkc.16G>C p.Glu6Gln missense_variant Exon 1 of 5 ENST00000255759.11 NP_653201.1 Q96NB1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CEP20ENST00000255759.11 linkc.16G>C p.Glu6Gln missense_variant Exon 1 of 5 1 NM_144600.4 ENSP00000255759.6 Q96NB1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.0000120
AC:
3
AN:
251028
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461860
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727236
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.0000671
AC:
3
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39698
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53412
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1111994
Other (OTH)
AF:
0.00
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
1
1
2
2
3
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
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 08, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.16G>C (p.E6Q) alteration is located in exon 1 (coding exon 1) of the FOPNL gene. This alteration results from a G to C substitution at nucleotide position 16, causing the glutamic acid (E) at amino acid position 6 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
Uncertain
0.41
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Pathogenic
0.21
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.068
T;.;.;T;T;T;T
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.87
D;D;D;T;D;D;T
M_CAP
Benign
0.032
D
MetaRNN
Uncertain
0.70
D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.072
T
MutationAssessor
Pathogenic
3.0
M;M;.;.;.;.;.
PhyloP100
4.0
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-2.1
N;.;.;.;.;.;.
REVEL
Benign
0.26
Sift
Uncertain
0.010
D;.;.;.;.;.;.
Sift4G
Uncertain
0.024
D;D;D;D;D;D;.
Polyphen
1.0
D;.;.;.;.;.;.
Vest4
0.46
MutPred
0.51
Gain of MoRF binding (P = 0.0281);Gain of MoRF binding (P = 0.0281);Gain of MoRF binding (P = 0.0281);Gain of MoRF binding (P = 0.0281);Gain of MoRF binding (P = 0.0281);Gain of MoRF binding (P = 0.0281);Gain of MoRF binding (P = 0.0281);
MVP
0.12
MPC
0.074
ClinPred
0.96
D
GERP RS
5.6
PromoterAI
-0.17
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.31
gMVP
0.59
Mutation Taster
=74/26
polymorphism

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

Other links and lift over

dbSNP: rs776955193; hg19: chr16-15982427; API