dbSNP rs17852716: OCLN:p.Leu233Ser (chr5-69509788-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001205254.2(OCLN):c.698T>C(p.Leu233Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L233L) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

OCLN
NM_001205254.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.21

Publications

0 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
pseudo-TORCH syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

OCLN links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.827

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205254.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OCLN	NM_001205254.2	MANE Select	c.698T>C	p.Leu233Ser	missense	Exon 3 of 9	NP_001192183.1	Q16625-1
OCLN	NM_001438604.1		c.698T>C	p.Leu233Ser	missense	Exon 3 of 9	NP_001425533.1
OCLN	NM_002538.4		c.698T>C	p.Leu233Ser	missense	Exon 3 of 9	NP_002529.1	Q16625-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OCLN	ENST00000396442.7	TSL:1 MANE Select	c.698T>C	p.Leu233Ser	missense	Exon 3 of 9	ENSP00000379719.2	Q16625-1
OCLN	ENST00000355237.6	TSL:1	c.698T>C	p.Leu233Ser	missense	Exon 3 of 9	ENSP00000347379.2	Q16625-1
OCLN	ENST00000538151.2	TSL:1	c.-24-4160T>C		intron	N/A	ENSP00000445940.1	Q16625-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

M_CAP

Benign

0.049

MetaRNN

Pathogenic

0.83

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.3

PhyloP100

6.2

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

Sift4G

Benign

0.12

Polyphen

1.0

Vest4

0.79

MutPred

0.68

Loss of stability (P = 0.0326)

MVP

0.61

MPC

0.42

ClinPred

1.0

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.80

gMVP

0.93

Mutation Taster

=33/67

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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