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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.:

GnomAD3 exomes

AF:

0.0000536

AC:

AN:

205170

Hom.:

AF XY:

0.0000888

AC XY:

AN XY:

112642

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:

0.000454

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000425

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000155

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Cov.:

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

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;.;.;.;.;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over