16-15879855-T-C

Variant names:

• chr16-15879855-T-C
• NM_144600.4:c.260A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144600.4(CEP20):​c.260A>G​(p.Gln87Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP20 NM_144600.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.67

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10556027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP20	NM_144600.4	c.260A>G	p.Gln87Arg	missense_variant	Exon 3 of 5	ENST00000255759.11	NP_653201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP20	ENST00000255759.11	c.260A>G	p.Gln87Arg	missense_variant	Exon 3 of 5	1	NM_144600.4	ENSP00000255759.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.260A>G (p.Q87R) alteration is located in exon 3 (coding exon 3) of the FOPNL gene. This alteration results from a A to G substitution at nucleotide position 260, causing the glutamine (Q) at amino acid position 87 to be replaced by an arginine (R). 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	0.087
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T;.;T;T;T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.87	D;T;T;D;T;D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.11	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.;.;.;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.6	N;.;.;.;.;.
REVEL	Benign	0.050
Sift	Benign	0.34	T;.;.;.;.;.
Sift4G	Benign	0.29	T;T;D;T;T;.
Polyphen		0.045	B;.;.;.;.;.
Vest4		0.26
MutPred		0.36		Loss of catalytic residue at Q87 (P = 0.0315);.;.;Loss of catalytic residue at Q87 (P = 0.0315);.;.;
MVP		0.10
MPC		0.016
ClinPred		0.26	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.039
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-15973712; COSMIC: COSV55385023; COSMIC: COSV55385023;