Genetic Variant CEP57L1:p.Val143Leu (chr6-109150204-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_001271852.3(CEP57L1):c.427G>T(p.Val143Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V143I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CEP57L1
NM_001271852.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.68

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=0.3113139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP57L1	NM_001271852.3 link	c.427G>T	p.Val143Leu	missense_variant	Exon 4 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.427G>T	p.Val143Leu	missense_variant	Exon 4 of 11	2	NM_001271852.3	ENSP00000427844.1		Q8IYX8-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152098

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251202

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135762

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.88e-7

AC:

AN:

1454310

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

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

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

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

M_CAP

Benign

0.030

MetaRNN

Benign

0.31

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

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

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

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.7

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

REVEL

Benign

0.17

Sift

Uncertain

0.027

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

Sift4G

Benign

0.14

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

Polyphen

0.64

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

Vest4

0.42

MutPred

0.48

.;Loss of methylation at K147 (P = 0.0757);Loss of methylation at K147 (P = 0.0757);Loss of methylation at K147 (P = 0.0757);Loss of methylation at K147 (P = 0.0757);Loss of methylation at K147 (P = 0.0757);Loss of methylation at K147 (P = 0.0757);.;Loss of methylation at K147 (P = 0.0757);Loss of methylation at K147 (P = 0.0757);.;.;Loss of methylation at K147 (P = 0.0757);.;.;Loss of methylation at K147 (P = 0.0757);

MVP

0.41

MPC

0.19

ClinPred

0.89

GERP RS

5.3

Varity_R

0.38

gMVP

0.28

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over