Genetic Variant CEP57L1:p.Arg19Lys (chr6-109145277-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 15/22 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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.049524486).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271852.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEP57L1	NM_001271852.3	MANE Select	c.56G>A	p.Arg19Lys	missense	Exon 2 of 11	NP_001258781.1	Q8IYX8-1
CEP57L1	NM_001350654.2		c.56G>A	p.Arg19Lys	missense	Exon 2 of 11	NP_001337583.1
CEP57L1	NM_001350655.2		c.56G>A	p.Arg19Lys	missense	Exon 3 of 12	NP_001337584.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEP57L1	ENST00000517392.6	TSL:2 MANE Select	c.56G>A	p.Arg19Lys	missense	Exon 2 of 11	ENSP00000427844.1	Q8IYX8-1
CEP57L1	ENST00000359793.7	TSL:1	c.56G>A	p.Arg19Lys	missense	Exon 2 of 11	ENSP00000352841.3	Q8IYX8-1
CEP57L1	ENST00000368970.6	TSL:5	c.56G>A	p.Arg19Lys	missense	Exon 2 of 11	ENSP00000357966.2	E5RFY4

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

GnomAD2 exomes

AF:

0.000144

AC:

AN:

249756

AF XY:

0.000148

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 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

African (AFR)

AF:

0.0000300

AC:

AN:

33294

American (AMR)

AF:

0.0000224

AC:

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.0000385

AC:

AN:

25998

East Asian (EAS)

AF:

0.00

AC:

AN:

39540

South Asian (SAS)

AF:

0.00

AC:

AN:

85770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5564

European-Non Finnish (NFE)

AF:

0.000501

AC:

554

AN:

1106364

Other (OTH)

AF:

0.000399

AC:

AN:

60092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

105

131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000263

AC:

AN:

151894

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41422

American (AMR)

AF:

0.000394

AC:

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000457

AC:

AN:

67860

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.0087

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.0046

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.67

M_CAP

Benign

0.0038

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

0.55

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.41

REVEL

Benign

0.053

Sift

Benign

0.71

Sift4G

Benign

1.0

Polyphen

0.0030

Vest4

0.15

MVP

0.36

MPC

0.044

ClinPred

0.038

GERP RS

4.5

Varity_R

0.060

gMVP

0.39

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over