Variant 6-109145255-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001271852.3(CEP57L1):c.34A>G(p.Ser12Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000827 in 1,596,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

CEP57L1
NM_001271852.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.50

Variant links:

Genes affected

CEP57L1 (HGNC:21561): (centrosomal protein 57 like 1) Enables identical protein binding activity. Predicted to be located in cytoplasm and microtubule. Predicted to be active in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

CEP57L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34184685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP57L1	NM_001271852.3 linkuse as main transcript	c.34A>G	p.Ser12Gly	missense_variant	2/11	ENST00000517392.6	NP_001258781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP57L1	ENST00000517392.6 linkuse as main transcript	c.34A>G	p.Ser12Gly	missense_variant	2/11	2	NM_001271852.3	ENSP00000427844		Q8IYX8-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

151958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000846

AC:

AN:

248118

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

134230

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000187

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000858

AC:

124

AN:

1444814

Hom.:

Cov.:

AF XY:

0.0000861

AC XY:

AN XY:

719694

show subpopulations

Gnomad4 AFR exome

AF:

0.0000607

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

AF:

0.0000526

AC:

AN:

151958

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000988

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2022

The c.34A>G (p.S12G) alteration is located in exon 4 (coding exon 1) of the CEP57L1 gene. This alteration results from a A to G substitution at nucleotide position 34, causing the serine (S) at amino acid position 12 to be replaced by a glycine (G). 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

0.26

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;T;T;T;.;.;T;.;T;T;T;T;.;T;T;T;T

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;.;D;D;D;D;D;D;D;D;D;.;D;D;D;D;D

M_CAP

Benign

0.077

MetaRNN

Benign

0.34

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.1

.;M;.;.;.;.;.;.;.;.;.;.;M;.;.;.;M

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;N;N

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.8

D;D;D;D;D;D;D;D;D;D;D;D;D;D;N;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0070

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.030

D;D;T;D;D;D;D;D;D;D;D;T;D;D;D;D;D

Polyphen

1.0

D;D;D;.;.;.;.;.;.;.;.;D;.;.;.;.;D

Vest4

0.71

MVP

0.73

MPC

0.18

ClinPred

0.52

GERP RS

5.4

Varity_R

0.66

gMVP

0.54

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