Variant 5-69534806-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001205254.2(OCLN):c.1004G>A(p.Arg335Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 18)

Exomes 𝑓: 0.00016 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

OCLN
NM_001205254.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.822

Variant links:

Genes affected

OCLN (HGNC:8104): (occludin) This gene encodes an integral membrane protein that is required for cytokine-induced regulation of the tight junction paracellular permeability barrier. Mutations in this gene are thought to be a cause of band-like calcification with simplified gyration and polymicrogyria (BLC-PMG), an autosomal recessive neurologic disorder that is also known as pseudo-TORCH syndrome. Alternative splicing results in multiple transcript variants. A related pseudogene is present 1.5 Mb downstream on the q arm of chromosome 5. [provided by RefSeq, Apr 2011]

OCLN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047424734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCLN	NM_001205254.2 linkuse as main transcript	c.1004G>A	p.Arg335Gln	missense_variant	5/9	ENST00000396442.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCLN	ENST00000396442.7 linkuse as main transcript	c.1004G>A	p.Arg335Gln	missense_variant	5/9	1	NM_001205254.2	P1	Q16625-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

165

AN:

123338

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00583

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000552

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00357

Gnomad NFE

AF:

0.0000485

Gnomad OTH

AF:

0.000600

GnomAD3 exomes

AF:

0.000263

AC:

AN:

239548

Hom.:

AF XY:

0.000230

AC XY:

AN XY:

130226

show subpopulations

Gnomad AFR exome

AF:

0.00456

Gnomad AMR exome

AF:

0.0000896

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000160

AC:

199

AN:

1246484

Hom.:

Cov.:

AF XY:

0.000126

AC XY:

AN XY:

628184

show subpopulations

Gnomad4 AFR exome

AF:

0.00652

Gnomad4 AMR exome

AF:

0.000279

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.000363

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00135

AC:

167

AN:

123410

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

AN XY:

59284

show subpopulations

Gnomad4 AFR

AF:

0.00588

Gnomad4 AMR

AF:

0.000552

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000485

Gnomad4 OTH

AF:

0.000592

Alfa

AF:

0.00144

Hom.:

ExAC

AF:

0.000250

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 17, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.088

T;T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.75

.;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.0047

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.20

N;N;N

REVEL

Benign

0.042

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.78

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.13

MVP

0.70

MPC

2.1

ClinPred

0.012

GERP RS

2.1

Varity_R

0.031

gMVP

0.36

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over