Genetic Variant NM_001042475.3:c.1600C>G (chr6-118481924-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001042475.3(CEP85L):c.1600C>G(p.Leu534Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000195 in 1,536,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CEP85L
NM_001042475.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

lissencephaly 10
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
lissencephaly due to LIS1 mutation
Inheritance: AD Classification: STRONG Submitted by: Illumina

CEP85L links:

ENSG00000303332 (HGNC:):

ENSG00000303332 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05797407).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042475.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP85L	NM_001042475.3	MANE Select	c.1600C>G	p.Leu534Val	missense	Exon 8 of 13	NP_001035940.1	Q5SZL2-1
	CEP85L	NM_001178035.2		c.1609C>G	p.Leu537Val	missense	Exon 9 of 14	NP_001171506.1	Q5SZL2-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEP85L	ENST00000368491.8	TSL:1 MANE Select	c.1600C>G	p.Leu534Val	missense	Exon 8 of 13	ENSP00000357477.3	Q5SZL2-1
CEP85L	ENST00000434604.5	TSL:1	c.1609C>G	p.Leu537Val	missense	Exon 9 of 9	ENSP00000392131.1	A2A3P3
CEP85L	ENST00000368488.9	TSL:5	c.1609C>G	p.Leu537Val	missense	Exon 9 of 14	ENSP00000357474.5	Q5SZL2-4

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

148134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000498

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000500

AC:

AN:

199814

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000394

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.20e-7

AC:

AN:

1388314

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30076

American (AMR)

AF:

0.0000277

AC:

AN:

36120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24446

East Asian (EAS)

AF:

0.00

AC:

AN:

37114

South Asian (SAS)

AF:

0.00

AC:

AN:

73036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5524

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074652

Other (OTH)

AF:

0.00

AC:

AN:

57024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000135

AC:

AN:

148134

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

71848

show subpopulations

African (AFR)

AF:

0.0000498

AC:

AN:

40162

American (AMR)

AF:

0.00

AC:

AN:

14732

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5040

South Asian (SAS)

AF:

0.00

AC:

AN:

4750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67410

Other (OTH)

AF:

0.00

AC:

AN:

2016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.0031

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.78

M_CAP

Benign

0.0095

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.48

PhyloP100

3.8

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.86

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

0.98

Polyphen

0.58

Vest4

0.30

MutPred

0.066

Gain of methylation at K537 (P = 0.2611)

MVP

0.22

MPC

0.29

ClinPred

0.16

GERP RS

3.5

Varity_R

0.058

gMVP

0.24

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over