Variant 6-109145237-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001271852.3(CEP57L1):c.16A>G(p.Met6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000546 in 1,577,578 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 1 hom. )

Consequence

CEP57L1
NM_001271852.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024120241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP57L1	NM_001271852.3 linkuse as main transcript	c.16A>G	p.Met6Val	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.16A>G	p.Met6Val	missense_variant	2/11	2	NM_001271852.3	ENSP00000427844		Q8IYX8-1

Frequencies

GnomAD3 genomes

AF:

0.000421

AC:

AN:

151952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

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:

0.000722

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000388

AC:

AN:

239384

Hom.:

AF XY:

0.000347

AC XY:

AN XY:

129642

show subpopulations

Gnomad AFR exome

AF:

0.000189

Gnomad AMR exome

AF:

0.0000630

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000946

Gnomad NFE exome

AF:

0.000779

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.000560

AC:

798

AN:

1425626

Hom.:

Cov.:

AF XY:

0.000528

AC XY:

375

AN XY:

710204

show subpopulations

Gnomad4 AFR exome

AF:

0.0000309

Gnomad4 AMR exome

AF:

0.0000701

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000945

Gnomad4 NFE exome

AF:

0.000707

Gnomad4 OTH exome

AF:

0.000356

GnomAD4 genome

AF:

0.000421

AC:

AN:

151952

Hom.:

Cov.:

AF XY:

0.000418

AC XY:

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000394

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000722

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000432

Hom.:

Bravo

AF:

0.000431

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000815

AC:

ExAC

AF:

0.000469

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

Aug 26, 2022

The c.16A>G (p.M6V) 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 16, causing the methionine (M) at amino acid position 6 to be replaced by a valine (V). 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

0.075

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.36

DEOGEN2

Benign

0.023

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

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.67

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

M_CAP

Benign

0.0091

MetaRNN

Benign

0.024

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L;.;.;.;.;.;.;.;.;.;.;L;.;.;.;L

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.2

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.054

Sift

Benign

0.15

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

Sift4G

Benign

0.083

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

Polyphen

0.017

B;B;B;.;.;.;.;.;.;.;.;B;.;.;.;.;B

Vest4

0.14

MVP

0.17

MPC

0.042

ClinPred

0.021

GERP RS

-1.6

Varity_R

0.062

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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