dbSNP rs61738593: CEP57L1:p.Val10Ile (chr6-109145249-G-A) – 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.28G>A(p.Val10Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,593,626 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CEP57L1
NM_001271852.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.911

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 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=0.041762173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP57L1	NM_001271852.3 link	c.28G>A	p.Val10Ile	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.28G>A	p.Val10Ile	missense_variant	Exon 2 of 11	2	NM_001271852.3	ENSP00000427844.1		Q8IYX8-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151774

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000282

AC:

AN:

247880

Hom.:

AF XY:

0.0000224

AC XY:

AN XY:

134090

show subpopulations

Gnomad AFR exome

AF:

0.0000620

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:

0.0000535

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000153

AC:

AN:

1441852

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

718414

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:

0.0000192

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151774

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74096

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:

0.0000295

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000494

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.8

DANN

Benign

0.72

DEOGEN2

Benign

0.0051

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

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.84

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

M_CAP

Benign

0.0054

MetaRNN

Benign

0.042

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

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

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.11

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

REVEL

Benign

0.026

Sift

Benign

0.69

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

Sift4G

Benign

1.0

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

Polyphen

0.0010

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

Vest4

0.10

MutPred

0.13

Loss of ubiquitination at K15 (P = 0.0982);Loss of ubiquitination at K15 (P = 0.0982);Loss of ubiquitination at K15 (P = 0.0982);Loss of ubiquitination at K15 (P = 0.0982);Loss of ubiquitination at K15 (P = 0.0982);Loss of ubiquitination at K15 (P = 0.0982);Loss of ubiquitination at K15 (P = 0.0982);Loss of ubiquitination at K15 (P = 0.0982);Loss of ubiquitination at K15 (P = 0.0982);Loss of ubiquitination at K15 (P = 0.0982);Loss of ubiquitination at K15 (P = 0.0982);Loss of ubiquitination at K15 (P = 0.0982);Loss of ubiquitination at K15 (P = 0.0982);Loss of ubiquitination at K15 (P = 0.0982);Loss of ubiquitination at K15 (P = 0.0982);.;Loss of ubiquitination at K15 (P = 0.0982);

MVP

0.25

MPC

0.038

ClinPred

0.030

GERP RS

2.1

Varity_R

0.028

gMVP

0.20

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