Variant 10-93519749-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018131.5(CEP55):c.1133A>T(p.His378Leu) variant causes a missense change. The variant allele was found at a frequency of 0.73 in 1,613,748 control chromosomes in the GnomAD database, including 439,066 homozygotes. In-silico tool predicts 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 0.63 ( 33484 hom., cov: 33)

Exomes 𝑓: 0.74 ( 405582 hom. )

Consequence

CEP55
NM_018131.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 6.13

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6668961E-6).

BP6

Variant 10-93519749-A-T is Benign according to our data. Variant chr10-93519749-A-T is described in ClinVar as [Benign]. Clinvar id is 1209684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP55	NM_018131.5 linkuse as main transcript	c.1133A>T	p.His378Leu	missense_variant	8/9	ENST00000371485.8	NP_060601.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP55	ENST00000371485.8 linkuse as main transcript	c.1133A>T	p.His378Leu	missense_variant	8/9	1	NM_018131.5	ENSP00000360540	P1	Q53EZ4-1
CEP55	ENST00000496302.1 linkuse as main transcript	n.182A>T		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.633

AC:

96234

AN:

151984

Hom.:

33467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.691

Gnomad AMR

AF:

0.732

Gnomad ASJ

AF:

0.761

Gnomad EAS

AF:

0.567

Gnomad SAS

AF:

0.678

Gnomad FIN

AF:

0.807

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.766

Gnomad OTH

AF:

0.687

GnomAD3 exomes

AF:

0.714

AC:

179525

AN:

251300

Hom.:

66113

AF XY:

0.722

AC XY:

98079

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.316

Gnomad AMR exome

AF:

0.757

Gnomad ASJ exome

AF:

0.761

Gnomad EAS exome

AF:

0.573

Gnomad SAS exome

AF:

0.692

Gnomad FIN exome

AF:

0.799

Gnomad NFE exome

AF:

0.766

Gnomad OTH exome

AF:

0.737

GnomAD4 exome

AF:

0.740

AC:

1082179

AN:

1461646

Hom.:

405582

Cov.:

AF XY:

0.741

AC XY:

538712

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.301

Gnomad4 AMR exome

AF:

0.753

Gnomad4 ASJ exome

AF:

0.761

Gnomad4 EAS exome

AF:

0.556

Gnomad4 SAS exome

AF:

0.693

Gnomad4 FIN exome

AF:

0.798

Gnomad4 NFE exome

AF:

0.762

Gnomad4 OTH exome

AF:

0.711

GnomAD4 genome

AF:

0.633

AC:

96262

AN:

152102

Hom.:

33484

Cov.:

AF XY:

0.637

AC XY:

47354

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.321

Gnomad4 AMR

AF:

0.732

Gnomad4 ASJ

AF:

0.761

Gnomad4 EAS

AF:

0.566

Gnomad4 SAS

AF:

0.677

Gnomad4 FIN

AF:

0.807

Gnomad4 NFE

AF:

0.766

Gnomad4 OTH

AF:

0.690

Alfa

AF:

0.738

Hom.:

29441

Bravo

AF:

0.610

TwinsUK

AF:

0.761

AC:

2822

ALSPAC

AF:

0.769

AC:

2964

ESP6500AA

AF:

0.328

AC:

1443

ESP6500EA

AF:

0.755

AC:

6494

ExAC

AF:

0.703

AC:

85369

Asia WGS

AF:

0.635

AC:

2208

AN:

3478

EpiCase

AF:

0.761

EpiControl

AF:

0.767

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

CEP55-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 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). -

Multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.039

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0000017

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.035

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.081

Sift

Benign

0.089

Sift4G

Uncertain

0.050

Polyphen

0.48

Vest4

0.18

MPC

0.25

ClinPred

0.026

GERP RS

5.8

Varity_R

0.099

gMVP

0.34

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

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