3-170432713-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005602.6(CLDN11):c.581C>A(p.Ala194Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. A194V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CLDN11
NM_005602.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.83

Publications

0 publications found

Variant links:

Genes affected

CLDN11 (HGNC:8514): (claudin 11) This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. The protein encoded by this gene is a major component of central nervous system (CNS) myelin and plays an important role in regulating proliferation and migration of oligodendrocytes. Mouse studies showed that the gene deficiency results in deafness and loss of the Sertoli cell epithelial phenotype in the testis. This protein is a tight junction protein at the human blood-testis barrier (BTB), and the BTB disruption is related to a dysfunction of this gene. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Aug 2010]

CLDN11 Gene-Disease associations (from GenCC):

leukodystrophy, hypomyelinating, 22
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

CLDN11 links:

ENSG00000285218 (HGNC:):

ENSG00000285218 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18153706).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005602.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN11	NM_005602.6	MANE Select	c.581C>A	p.Ala194Glu	missense	Exon 3 of 3	NP_005593.2
	CLDN11	NM_001185056.2		c.329C>A	p.Ala110Glu	missense	Exon 3 of 3	NP_001171985.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLDN11	ENST00000064724.8	TSL:1 MANE Select	c.581C>A	p.Ala194Glu	missense	Exon 3 of 3	ENSP00000064724.4	O75508
ENSG00000285218	ENST00000486975.1	TSL:2	c.391+9386C>A		intron	N/A	ENSP00000417434.1	B4DFI2
CLDN11	ENST00000970096.1		c.581C>A	p.Ala194Glu	missense	Exon 3 of 4	ENSP00000640155.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251488

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.23

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.087

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.71

M_CAP

Benign

0.036

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.50

MutationAssessor

Benign

0.34

PhyloP100

3.8

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.87

REVEL

Uncertain

0.32

Sift

Benign

0.21

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.14

MutPred

0.37

Loss of sheet (P = 0.0037)

MVP

0.88

MPC

0.69

ClinPred

0.32

GERP RS

5.8

Varity_R

0.16

gMVP

0.57

Mutation Taster

=54/46

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over