Genetic Variant CEP85L:p.Ser137Gly (chr6-118566140-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001042475.3(CEP85L):c.409A>G(p.Ser137Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,613,772 control chromosomes in the GnomAD database, including 219,199 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.51 ( 20040 hom., cov: 31)

Exomes 𝑓: 0.52 ( 199159 hom. )

Consequence

CEP85L
NM_001042475.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.111

Variant links:

Genes affected

CEP85L (HGNC:21638): (centrosomal protein 85 like) The protein encoded by this gene was identified as a breast cancer antigen. Nothing more is known of its function at this time. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

CEP85L links:

ENSG00000286339 (HGNC:):

ENSG00000286339 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.8026297E-5).

BP6

Variant 6-118566140-T-C is Benign according to our data. Variant chr6-118566140-T-C is described in ClinVar as [Benign]. Clinvar id is 1209727.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP85L	NM_001042475.3 link	c.409A>G	p.Ser137Gly	missense_variant	Exon 3 of 13	ENST00000368491.8	NP_001035940.1	Q5SZL2-1Q3ZCQ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP85L	ENST00000368491.8 link	c.409A>G	p.Ser137Gly	missense_variant	Exon 3 of 13	1	NM_001042475.3	ENSP00000357477.3		Q5SZL2-1

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

77067

AN:

151844

Hom.:

20031

Cov.:

show subpopulations

Gnomad AFR

AF:

0.553

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.282

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.522

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.540

Gnomad OTH

AF:

0.469

GnomAD3 exomes

AF:

0.467

AC:

117525

AN:

251412

Hom.:

29474

AF XY:

0.477

AC XY:

64855

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.554

Gnomad AMR exome

AF:

0.223

Gnomad ASJ exome

AF:

0.445

Gnomad EAS exome

AF:

0.281

Gnomad SAS exome

AF:

0.491

Gnomad FIN exome

AF:

0.525

Gnomad NFE exome

AF:

0.542

Gnomad OTH exome

AF:

0.496

GnomAD4 exome

AF:

0.516

AC:

754629

AN:

1461810

Hom.:

199159

Cov.:

AF XY:

0.516

AC XY:

375300

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.545

Gnomad4 AMR exome

AF:

0.238

Gnomad4 ASJ exome

AF:

0.444

Gnomad4 EAS exome

AF:

0.257

Gnomad4 SAS exome

AF:

0.491

Gnomad4 FIN exome

AF:

0.528

Gnomad4 NFE exome

AF:

0.539

Gnomad4 OTH exome

AF:

0.505

GnomAD4 genome

AF:

0.507

AC:

77106

AN:

151962

Hom.:

20040

Cov.:

AF XY:

0.500

AC XY:

37096

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.553

Gnomad4 AMR

AF:

0.334

Gnomad4 ASJ

AF:

0.446

Gnomad4 EAS

AF:

0.282

Gnomad4 SAS

AF:

0.485

Gnomad4 FIN

AF:

0.522

Gnomad4 NFE

AF:

0.540

Gnomad4 OTH

AF:

0.469

Alfa

AF:

0.517

Hom.:

38985

Bravo

AF:

0.492

TwinsUK

AF:

0.534

AC:

1981

ALSPAC

AF:

0.557

AC:

2146

ESP6500AA

AF:

0.552

AC:

2432

ESP6500EA

AF:

0.527

AC:

4529

ExAC

AF:

0.485

AC:

58930

Asia WGS

AF:

0.377

AC:

1311

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Lissencephaly 10

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.3

DANN

Benign

0.63

DEOGEN2

Benign

0.0037

T;.;T;.;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.39

T;T;T;T;T;T

MetaRNN

Benign

0.000048

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.0

L;.;.;.;.;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.76

N;N;N;N;N;N

REVEL

Benign

0.012

Sift

Benign

0.59

T;T;T;T;T;T

Sift4G

Benign

0.38

T;T;.;T;T;T

Polyphen

0.0

B;.;.;.;B;.

Vest4

0.049

MPC

0.071

ClinPred

0.0063

GERP RS

-2.6

Varity_R

0.041

gMVP

0.091

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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