Genetic Variant CEP57L1:p.Asn38Asp (chr6-109145333-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001271852.3(CEP57L1):c.112A>G(p.Asn38Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,764 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CEP57L1
NM_001271852.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.93

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=0.063788325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP57L1	NM_001271852.3 link	c.112A>G	p.Asn38Asp	missense_variant	Exon 2 of 11	ENST00000517392.6	NP_001258781.1	Q8IYX8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP57L1	ENST00000517392.6 link	c.112A>G	p.Asn38Asp	missense_variant	Exon 2 of 11	2	NM_001271852.3	ENSP00000427844.1		Q8IYX8-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250334

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135360

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459764

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000469

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.112A>G (p.N38D) 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 112, causing the asparagine (N) at amino acid position 38 to be replaced by an aspartic acid (D). 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

0.071

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.7

DANN

Benign

0.36

DEOGEN2

Benign

0.026

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

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.70

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

M_CAP

Benign

0.0068

MetaRNN

Benign

0.064

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

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

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.79

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

REVEL

Benign

0.030

Sift

Benign

0.74

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

Sift4G

Benign

0.73

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

Polyphen

0.0020

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

Vest4

0.22

MutPred

0.14

Loss of catalytic residue at N38 (P = 0.1728);Loss of catalytic residue at N38 (P = 0.1728);Loss of catalytic residue at N38 (P = 0.1728);Loss of catalytic residue at N38 (P = 0.1728);Loss of catalytic residue at N38 (P = 0.1728);Loss of catalytic residue at N38 (P = 0.1728);Loss of catalytic residue at N38 (P = 0.1728);Loss of catalytic residue at N38 (P = 0.1728);Loss of catalytic residue at N38 (P = 0.1728);Loss of catalytic residue at N38 (P = 0.1728);Loss of catalytic residue at N38 (P = 0.1728);Loss of catalytic residue at N38 (P = 0.1728);Loss of catalytic residue at N38 (P = 0.1728);Loss of catalytic residue at N38 (P = 0.1728);.;Loss of catalytic residue at N38 (P = 0.1728);

MVP

0.28

MPC

0.047

ClinPred

0.0081

GERP RS

3.2

Varity_R

0.052

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

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