NM_018131.5:c.171C>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018131.5(CEP55):c.171C>G(p.His57Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,607,764 control chromosomes in the GnomAD database, including 41,389 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.24 ( 4363 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37026 hom. )

Consequence

CEP55
NM_018131.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.448

Variant links:

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]

CEP55 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036286712).

BP6

Variant 10-93500222-C-G is Benign according to our data. Variant chr10-93500222-C-G is described in ClinVar as [Benign]. Clinvar id is 1593062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP55	NM_018131.5 link	c.171C>G	p.His57Gln	missense_variant	Exon 2 of 9	ENST00000371485.8	NP_060601.4	Q53EZ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP55	ENST00000371485.8 link	c.171C>G	p.His57Gln	missense_variant	Exon 2 of 9	1	NM_018131.5	ENSP00000360540.3		Q53EZ4-1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35899

AN:

151932

Hom.:

4357

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.222

Gnomad OTH

AF:

0.242

GnomAD3 exomes

AF:

0.218

AC:

54051

AN:

247410

Hom.:

6339

AF XY:

0.225

AC XY:

30194

AN XY:

133922

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.300

Gnomad EAS exome

AF:

0.286

Gnomad SAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.217

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

AF:

0.222

AC:

322894

AN:

1455714

Hom.:

37026

Cov.:

AF XY:

0.225

AC XY:

162889

AN XY:

724400

show subpopulations

Gnomad4 AFR exome

AF:

0.286

Gnomad4 AMR exome

AF:

0.123

Gnomad4 ASJ exome

AF:

0.303

Gnomad4 EAS exome

AF:

0.279

Gnomad4 SAS exome

AF:

0.270

Gnomad4 FIN exome

AF:

0.183

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.232

GnomAD4 genome

AF:

0.236

AC:

35924

AN:

152050

Hom.:

4363

Cov.:

AF XY:

0.236

AC XY:

17518

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.283

Gnomad4 AMR

AF:

0.172

Gnomad4 ASJ

AF:

0.308

Gnomad4 EAS

AF:

0.277

Gnomad4 SAS

AF:

0.273

Gnomad4 FIN

AF:

0.179

Gnomad4 NFE

AF:

0.222

Gnomad4 OTH

AF:

0.242

Alfa

AF:

0.233

Hom.:

3234

Bravo

AF:

0.236

TwinsUK

AF:

0.219

AC:

812

ALSPAC

AF:

0.214

AC:

823

ESP6500AA

AF:

0.287

AC:

1263

ESP6500EA

AF:

0.227

AC:

1955

ExAC

AF:

0.225

AC:

27283

Asia WGS

AF:

0.261

AC:

905

AN:

3478

EpiCase

AF:

0.234

EpiControl

AF:

0.232

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

CEP55-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.0020

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0036

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.31

PROVEAN

Benign

0.24

REVEL

Benign

0.054

Sift

Benign

0.66

Sift4G

Benign

0.56

Polyphen

0.0010

Vest4

0.040

MutPred

0.31

Gain of MoRF binding (P = 0.0905);

MPC

0.15

ClinPred

0.00030

GERP RS

-1.1

Varity_R

0.034

gMVP

0.049

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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