rs201673353

chr5-69534806-G-Achr5-69534806-G-T

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. 15/20 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.822

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]

ACMG classification

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	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	c.1004G>A	p.Arg335Gln	missense_variant	5/9	1	NM_001205254.2	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 165 AN: 123338 Hom.: 0 Cov.: 18 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: 63 AN: 239548 Hom.: 0 AF XY: 0.000230 AC XY: 30 AN XY: 130226

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.: 1 Cov.: 19 AF XY: 0.000126 AC XY: 79 AN XY: 628184

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.: 0 Cov.: 18 AF XY: 0.00116 AC XY: 69 AN XY: 59284

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.: 0

ExAC AF: 0.000250 AC: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	17
Dann	Benign	0.96
DEOGEN2	Benign	0.088	T;T;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.060	N
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.0047	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.30	T
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	T
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

Other links and lift over

dbSNP: rs201673353; hg19: chr5-68830633; COSMIC: COSV62285575; COSMIC: COSV62285575;