Genetic Variant CEP20:p.Pro83Ser (chr16-15879868-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_144600.4(CEP20):c.247C>T(p.Pro83Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000367 in 1,417,052 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000037 ( 1 hom. )

Consequence

CEP20
NM_144600.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15

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]

CEP20 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.30662772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP20	NM_144600.4 link	c.247C>T	p.Pro83Ser	missense_variant	Exon 3 of 5	ENST00000255759.11	NP_653201.1	Q96NB1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP20	ENST00000255759.11 link	c.247C>T	p.Pro83Ser	missense_variant	Exon 3 of 5	1	NM_144600.4	ENSP00000255759.6		Q96NB1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000536

AC:

AN:

205170

AF XY:

0.0000888

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000367

AC:

AN:

1417052

Hom.:

Cov.:

AF XY:

0.0000482

AC XY:

AN XY:

705320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29456

American (AMR)

AF:

0.00

AC:

AN:

32158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25056

East Asian (EAS)

AF:

0.00

AC:

AN:

35912

South Asian (SAS)

AF:

0.000425

AC:

AN:

79990

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.0000155

AC:

AN:

1097754

Other (OTH)

AF:

0.0000171

AC:

AN:

58558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 30, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.247C>T (p.P83S) alteration is located in exon 3 (coding exon 3) of the FOPNL gene. This alteration results from a C to T substitution at nucleotide position 247, causing the proline (P) at amino acid position 83 to be replaced by a serine (S). 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

0.24

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.;T;T;T;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;T;D;D;T;D

M_CAP

Benign

0.0051

MetaRNN

Benign

0.31

T;T;T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

2.0

M;.;.;.;.;.

PhyloP100

6.2

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-5.6

D;.;.;.;.;.

REVEL

Uncertain

0.31

Sift

Benign

0.071

T;.;.;.;.;.

Sift4G

Benign

0.090

T;T;D;T;T;.

Polyphen

0.93

P;.;.;.;.;.

Vest4

0.25

MutPred

0.62

Loss of loop (P = 0.1242);.;.;Loss of loop (P = 0.1242);.;.;

MVP

0.25

MPC

0.056

ClinPred

0.42

GERP RS

5.9

Varity_R

0.33

gMVP

0.37

Mutation Taster

=46/54

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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16-15879868-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over