10-93500222-C-G

Position:

• chr10-93500222-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.24 (4363 hom., cov: 32)
  • Exomes 𝑓: 0.22 (37026 hom.)
• Consequence: CEP55 NM_018131.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.448

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 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/exons	MANE	UniProt
CEP55	NM_018131.5	c.171C>G	p.His57Gln	missense_variant	2/9	ENST00000371485.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP55	ENST00000371485.8	c.171C>G	p.His57Gln	missense_variant	2/9	1	NM_018131.5	P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35899 AN: 151932 Hom.: 4357 Cov.: 32

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

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.: 31 AF XY: 0.225 AC XY: 162889 AN XY: 724400

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.: 32 AF XY: 0.236 AC XY: 17518 AN XY: 74318

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

CEP55-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	13
DANN	Benign	0.81
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.054
Sift	Benign	0.66	T
Sift4G	Benign	0.56	T
Polyphen		0.0010	B
Vest4		0.040
MutPred		0.31		Gain of MoRF binding (P = 0.0905);
MPC		0.15
ClinPred		0.00030	T
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

Other links and lift over

dbSNP: rs3740370; hg19: chr10-95259979; COSMIC: COSV65184504;