3-170432754-T-G

Variant names:

• chr3-170432754-T-G
• rs2108249442
• NM_005602.6:c.622T>G

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_005602.6(CLDN11):​c.622T>G​(p.Ter208Gluext*?) variant causes a stop lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CLDN11 NM_005602.6 stop_lost
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.33
• Publications: 1 publications found

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)

ENSG00000285218 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_005602.6 Downstream stopcodon found after 273 codons.
• PP5: Variant 3-170432754-T-G is Pathogenic according to our data. Variant chr3-170432754-T-G is described in ClinVar as Pathogenic. ClinVar VariationId is 1106670.Status of the report is no_assertion_criteria_provided, 0 stars.

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.622T>G	p.Ter208Gluext*?	stop_lost	Exon 3 of 3	NP_005593.2
	CLDN11	NM_001185056.2		c.370T>G	p.Ter124Gluext*?	stop_lost	Exon 3 of 3	NP_001171985.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN11	ENST00000064724.8	TSL:1 MANE Select	c.622T>G	p.Ter208Gluext*?	stop_lost	Exon 3 of 3	ENSP00000064724.4	O75508
	ENSG00000285218	ENST00000486975.1	TSL:2	c.391+9427T>G		intron	N/A	ENSP00000417434.1	B4DFI2
	CLDN11	ENST00000970096.1		c.622T>G	p.Ter208Gluext*?	stop_lost	Exon 3 of 4	ENSP00000640155.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Leukodystrophy, hypomyelinating, 22 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.78
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	1.0	D
PhyloP100		7.3
Vest4		0.050
GERP RS		5.8
Mutation Taster		=59/41	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

Other links and lift over

dbSNP: rs2108249442; hg19: chr3-170150542;