Variant chr5-69534806-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001205254.2(OCLN):c.1004G>T(p.Arg335Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R335Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 18)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OCLN
NM_001205254.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10387504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCLN	NM_001205254.2 linkuse as main transcript	c.1004G>T	p.Arg335Leu	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>T	p.Arg335Leu	missense_variant	5/9	1	NM_001205254.2	P1	Q16625-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

123556

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000160

AC:

AN:

1246844

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

628336

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000215

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

123556

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

59278

Gnomad4 AFR

AF:

0.00

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

0.0083

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.81

.;T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.8

L;L;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.68

N;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.023

D;D;T

Sift4G

Benign

0.45

T;T;T

Polyphen

0.0050

B;B;.

Vest4

0.34

MutPred

0.29

Loss of methylation at K334 (P = 0.065);Loss of methylation at K334 (P = 0.065);.;

MVP

0.72

MPC

2.4

ClinPred

0.22

GERP RS

2.1

Varity_R

0.072

gMVP

0.50

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over