Variant 6-118481924-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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. 12/20 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

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:

LOC105377971 (HGNC:):

LOC105377971 links:

Genome browser will be placed here

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=0.05797407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP85L	NM_001042475.3 linkuse as main transcript	c.1600C>G	p.Leu534Val	missense_variant	8/13	ENST00000368491.8
LOC105377971	XR_001743824.3 linkuse as main transcript	n.139-186G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP85L	ENST00000368491.8 linkuse as main transcript	c.1600C>G	p.Leu534Val	missense_variant	8/13	1	NM_001042475.3	P1	Q5SZL2-1
CEP85L	ENST00000434604.5 linkuse as main transcript	c.1609C>G	p.Leu537Val	missense_variant	9/9	1
CEP85L	ENST00000368488.9 linkuse as main transcript	c.1609C>G	p.Leu537Val	missense_variant	9/14	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

GnomAD3 exomes

AF:

0.00000500

AC:

AN:

199814

Hom.:

AF XY:

0.00

AC XY:

AN XY:

108900

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000277

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:

0.00

GnomAD4 genome

AF:

0.0000135

AC:

AN:

148134

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

71848

show subpopulations

Gnomad4 AFR

AF:

0.0000498

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 21, 2021

The c.1600C>G (p.L534V) alteration is located in exon 8 (coding exon 8) of the CEP85L gene. This alteration results from a C to G substitution at nucleotide position 1600, causing the leucine (L) at amino acid position 534 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.49

Cadd

Benign

Dann

Benign

0.47

DEOGEN2

Benign

0.0031

T;.;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.058

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.48

N;.;.

MutationTaster

Benign

0.89

N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.86

N;N;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.98

T;T;.

Polyphen

0.58

P;.;.

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

Splicing

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