NM_001205254.2:c.1004G>T

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.822

Publications

3 publications found
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 Gene-Disease associations (from GenCC):
  • pseudo-TORCH syndrome 1
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • pseudo-TORCH syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (MetaRNN=0.10387504).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OCLNNM_001205254.2 linkc.1004G>T p.Arg335Leu missense_variant Exon 5 of 9 ENST00000396442.7 NP_001192183.1 Q16625-1A8K3T2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OCLNENST00000396442.7 linkc.1004G>T p.Arg335Leu missense_variant Exon 5 of 9 1 NM_001205254.2 ENSP00000379719.2 Q16625-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
123556
Hom.:
0
Cov.:
18
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:
2
AN:
1246844
Hom.:
0
Cov.:
19
AF XY:
0.00
AC XY:
0
AN XY:
628336
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
23126
American (AMR)
AF:
0.00
AC:
0
AN:
43040
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23788
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38834
South Asian (SAS)
AF:
0.00
AC:
0
AN:
80662
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52156
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4700
European-Non Finnish (NFE)
AF:
0.00000215
AC:
2
AN:
928110
Other (OTH)
AF:
0.00
AC:
0
AN:
52428
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000081), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.300
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
123556
Hom.:
0
Cov.:
18
AF XY:
0.00
AC XY:
0
AN XY:
59278
African (AFR)
AF:
0.00
AC:
0
AN:
26466
American (AMR)
AF:
0.00
AC:
0
AN:
12684
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3146
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4566
South Asian (SAS)
AF:
0.00
AC:
0
AN:
3676
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
8370
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
280
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
61866
Other (OTH)
AF:
0.00
AC:
0
AN:
1668
Alfa
AF:
0.00
Hom.:
1

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
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T;T;.
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.60
FATHMM_MKL
Benign
0.076
N
LIST_S2
Benign
0.81
.;T;T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.10
T;T;T
MetaSVM
Benign
-0.60
T
MutationAssessor
Benign
1.8
L;L;.
PhyloP100
0.82
PrimateAI
Benign
0.34
T
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
T
GERP RS
2.1
Varity_R
0.072
gMVP
0.50
Mutation Taster
=84/16
polymorphism

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

Other links and lift over

dbSNP: rs201673353; hg19: chr5-68830633; API