Variant 6-109145277-G-A 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.56G>A(p.Arg19Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000387 in 1,606,478 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 1 hom. )

Consequence

CEP57L1
NM_001271852.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.553

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:

CEP57L1 (HGNC:):

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=0.049524486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP57L1	NM_001271852.3 linkuse as main transcript	c.56G>A	p.Arg19Lys	missense_variant	2/11	ENST00000517392.6	NP_001258781.1	Q8IYX8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP57L1	ENST00000517392.6 linkuse as main transcript	c.56G>A	p.Arg19Lys	missense_variant	2/11	2	NM_001271852.3	ENSP00000427844.1		Q8IYX8-1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

151894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000457

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000144

AC:

AN:

249756

Hom.:

AF XY:

0.000148

AC XY:

AN XY:

135050

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000873

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:

0.000275

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000399

AC:

581

AN:

1454584

Hom.:

Cov.:

AF XY:

0.000398

AC XY:

288

AN XY:

724010

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000501

Gnomad4 OTH exome

AF:

0.000399

GnomAD4 genome

AF:

0.000263

AC:

AN:

151894

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74170

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.000457

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000430

Hom.:

Bravo

AF:

0.000280

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000165

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

Sep 30, 2021

The c.56G>A (p.R19K) alteration is located in exon 4 (coding exon 1) of the CEP57L1 gene. This alteration results from a G to A substitution at nucleotide position 56, causing the arginine (R) at amino acid position 19 to be replaced by a lysine (K). 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

0.080

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.49

DEOGEN2

Benign

0.0087

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

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.0046

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.67

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

M_CAP

Benign

0.0038

MetaRNN

Benign

0.050

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

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

MutationTaster

Benign

0.99

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

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.41

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

REVEL

Benign

0.053

Sift

Benign

0.71

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

Sift4G

Benign

1.0

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

Polyphen

0.0030

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

Vest4

0.15

MVP

0.36

MPC

0.044

ClinPred

0.038

GERP RS

4.5

Varity_R

0.060

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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