11-95821969-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_014679.5(CEP57):c.798A>G(p.Pro266Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 1,610,584 control chromosomes in the GnomAD database, including 1,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 87 hom., cov: 32)

Exomes 𝑓: 0.033 ( 937 hom. )

Consequence

CEP57
NM_014679.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.79

Variant links:

Genes affected

CEP57 (HGNC:30794): (centrosomal protein 57) This gene encodes a cytoplasmic protein called Translokin. This protein localizes to the centrosome and has a function in microtubular stabilization. The N-terminal half of this protein is required for its centrosome localization and for its multimerization, and the C-terminal half is required for nucleating, bundling and anchoring microtubules to the centrosomes. This protein specifically interacts with fibroblast growth factor 2 (FGF2), sorting nexin 6, Ran-binding protein M and the kinesins KIF3A and KIF3B, and thus mediates the nuclear translocation and mitogenic activity of the FGF2. It also interacts with cyclin D1 and controls nucleocytoplasmic distribution of the cyclin D1 in quiescent cells. This protein is crucial for maintaining correct chromosomal number during cell division. Mutations in this gene cause mosaic variegated aneuploidy syndrome, a rare autosomal recessive disorder. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

CEP57 links:

MTMR2 (HGNC:7450): (myotubularin related protein 2) This gene is a member of the myotubularin family of phosphoinositide lipid phosphatases. The encoded protein possesses phosphatase activity towards phosphatidylinositol-3-phosphate and phosphatidylinositol-3,5-bisphosphate. Mutations in this gene are a cause of Charcot-Marie-Tooth disease type 4B, an autosomal recessive demyelinating neuropathy. Alternatively spliced transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

MTMR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 11-95821969-A-G is Benign according to our data. Variant chr11-95821969-A-G is described in ClinVar as [Benign]. Clinvar id is 414983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.79 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP57	NM_014679.5 link	c.798A>G	p.Pro266Pro	synonymous_variant	Exon 7 of 11	ENST00000325542.10	NP_055494.2	Q86XR8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP57	ENST00000325542.10 link	c.798A>G	p.Pro266Pro	synonymous_variant	Exon 7 of 11	1	NM_014679.5	ENSP00000317902.5		Q86XR8-1

Frequencies

GnomAD3 genomes

AF:

0.0290

AC:

4411

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00937

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0361

Gnomad ASJ

AF:

0.0553

Gnomad EAS

AF:

0.000961

Gnomad SAS

AF:

0.0135

Gnomad FIN

AF:

0.0486

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0377

Gnomad OTH

AF:

0.0415

GnomAD3 exomes

AF:

0.0324

AC:

8079

AN:

249316

Hom.:

160

AF XY:

0.0328

AC XY:

4425

AN XY:

134896

show subpopulations

Gnomad AFR exome

AF:

0.00728

Gnomad AMR exome

AF:

0.0248

Gnomad ASJ exome

AF:

0.0646

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.0156

Gnomad FIN exome

AF:

0.0493

Gnomad NFE exome

AF:

0.0414

Gnomad OTH exome

AF:

0.0439

GnomAD4 exome

AF:

0.0332

AC:

48485

AN:

1458348

Hom.:

937

Cov.:

AF XY:

0.0333

AC XY:

24138

AN XY:

725632

show subpopulations

Gnomad4 AFR exome

AF:

0.00856

Gnomad4 AMR exome

AF:

0.0256

Gnomad4 ASJ exome

AF:

0.0674

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0158

Gnomad4 FIN exome

AF:

0.0519

Gnomad4 NFE exome

AF:

0.0348

Gnomad4 OTH exome

AF:

0.0361

GnomAD4 genome

AF:

0.0290

AC:

4414

AN:

152236

Hom.:

Cov.:

AF XY:

0.0293

AC XY:

2184

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00936

Gnomad4 AMR

AF:

0.0360

Gnomad4 ASJ

AF:

0.0553

Gnomad4 EAS

AF:

0.000963

Gnomad4 SAS

AF:

0.0135

Gnomad4 FIN

AF:

0.0486

Gnomad4 NFE

AF:

0.0377

Gnomad4 OTH

AF:

0.0411

Alfa

AF:

0.0359

Hom.:

Bravo

AF:

0.0272

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0417

EpiControl

AF:

0.0442

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mosaic variegated aneuploidy syndrome 2

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

CEP57-related disorder

Benign:1

Mar 06, 2024

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

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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