Variant 6-109155302-T-C 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.652T>C(p.Ser218Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CEP57L1
NM_001271852.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78

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:

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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=0.3404138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP57L1	NM_001271852.3 linkuse as main transcript	c.652T>C	p.Ser218Pro	missense_variant	6/11	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.652T>C	p.Ser218Pro	missense_variant	6/11	2	NM_001271852.3	ENSP00000427844		Q8IYX8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.07e-7

AC:

AN:

1414518

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

704592

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000260

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.:

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

May 03, 2023

The c.652T>C (p.S218P) alteration is located in exon 8 (coding exon 5) of the CEP57L1 gene. This alteration results from a T to C substitution at nucleotide position 652, causing the serine (S) at amino acid position 218 to be replaced by a proline (P). 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

Pathogenic

0.79

BayesDel_addAF

Uncertain

0.063

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.079

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

Eigen

Benign

-0.096

Eigen_PC

Benign

-0.044

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.74

T;.;D;D;T;.;D;D;D;T;D;D;D

M_CAP

Benign

0.056

MetaRNN

Benign

0.34

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

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.69

.;N;.;.;.;.;N;.;.;.;.;.;N

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.5

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

REVEL

Uncertain

0.30

Sift

Uncertain

0.011

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

Sift4G

Benign

0.079

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

Polyphen

0.75

P;P;P;.;.;P;.;.;.;.;.;.;P

Vest4

0.34

MutPred

0.45

.;Loss of phosphorylation at S218 (P = 0.0855);Loss of phosphorylation at S218 (P = 0.0855);Loss of phosphorylation at S218 (P = 0.0855);Loss of phosphorylation at S218 (P = 0.0855);Loss of phosphorylation at S218 (P = 0.0855);Loss of phosphorylation at S218 (P = 0.0855);.;.;Loss of phosphorylation at S218 (P = 0.0855);.;.;Loss of phosphorylation at S218 (P = 0.0855);

MVP

0.77

MPC

0.26

ClinPred

0.65

GERP RS

1.2

Varity_R

0.51

gMVP

0.36

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