10-93500068-C-G

Position:

• chr10-93500068-C-G

Variant summary

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

The NM_018131.5(CEP55):​c.17C>G​(p.Thr6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CEP55 NM_018131.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.26

Genes affected

CEP55 (HGNC:1161): (centrosomal protein 55) Enables identical protein binding activity. Involved in cranial skeletal system development; establishment of protein localization; and midbody abscission. Acts upstream of or within mitotic cytokinesis. Located in Flemming body; centriolar satellite; and plasma membrane. Implicated in multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly. [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=0.093088746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP55	NM_018131.5	c.17C>G	p.Thr6Ser	missense_variant	2/9	ENST00000371485.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP55	ENST00000371485.8	c.17C>G	p.Thr6Ser	missense_variant	2/9	1	NM_018131.5	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.17C>G (p.T6S) alteration is located in exon 2 (coding exon 1) of the CEP55 gene. This alteration results from a C to G substitution at nucleotide position 17, causing the threonine (T) at amino acid position 6 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	0.083
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.019
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N
MutationTaster	Benign	0.96	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.079
Sift	Benign	0.29	T
Sift4G	Benign	0.24	T
Polyphen		0.034	B
Vest4		0.087
MutPred		0.29		Gain of relative solvent accessibility (P = 0.1259);
MVP		0.18
MPC		0.13
ClinPred		0.56	D
GERP RS		5.2
Varity_R		0.11
gMVP		0.11

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: chr10-95259825;