14-80756918-G-A

Position:

• chr14-80756918-G-A

Variant summary

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

The NM_152446.5(CEP128):​c.2587C>T​(p.Pro863Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000276 in 1,448,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: CEP128 NM_152446.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73

Genes affected

CEP128 (HGNC:20359): (centrosomal protein 128) Involved in protein localization. Located in centriole and spindle pole. Part of centriolar subdistal appendage. [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=0.12996525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP128	NM_152446.5	c.2587C>T	p.Pro863Ser	missense_variant	18/25	ENST00000555265.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP128	ENST00000555265.6	c.2587C>T	p.Pro863Ser	missense_variant	18/25	5	NM_152446.5	P2
CEP128	ENST00000281129.7	c.2587C>T	p.Pro863Ser	missense_variant	17/24	1		P2
CEP128	ENST00000554728.1	c.190C>T	p.Pro64Ser	missense_variant	2/3	2
CEP128	ENST00000554502.5	c.1663C>T	p.Pro555Ser	missense_variant, NMD_transcript_variant	7/15	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1448228 Hom.: 0 Cov.: 26 AF XY: 0.00000277 AC XY: 2 AN XY: 721316

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000363

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 17, 2023

The c.2587C>T (p.P863S) alteration is located in exon 17 (coding exon 16) of the CEP128 gene. This alteration results from a C to T substitution at nucleotide position 2587, causing the proline (P) at amino acid position 863 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	0.30
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Benign	0.26
DEOGEN2	Benign	0.043	T;T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.77	T;.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;.
MutationTaster	Benign	0.96	N;N
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.5	N;N;D
REVEL	Benign	0.049
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.44	T;T;D
Polyphen		0.075	B;B;.
Vest4		0.55
MutPred		0.39		Gain of catalytic residue at D862 (P = 0);Gain of catalytic residue at D862 (P = 0);.;
MVP		0.28
MPC		0.089
ClinPred		0.35	T
GERP RS		3.5
Varity_R		0.059
gMVP		0.36

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

LitVar

Other links and lift over

dbSNP: rs1340029638; hg19: chr14-81223262;