rs10513681

Variant names:

• chr3-170423520-T-C
• rs10513681
• NM_005602.6:c.391+193T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005602.6(CLDN11):​c.391+193T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0312 in 580,924 control chromosomes in the GnomAD database, including 1,056 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.064 (739 hom., cov: 32)
  • Exomes 𝑓: 0.020 (317 hom.)
• Consequence: CLDN11 NM_005602.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

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.391+193T>C		intron	N/A	NP_005593.2
	CLDN11	NM_001185056.2		c.139+193T>C		intron	N/A	NP_001171985.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN11	ENST00000064724.8	TSL:1 MANE Select	c.391+193T>C		intron	N/A	ENSP00000064724.4	O75508
	ENSG00000285218	ENST00000486975.1	TSL:2	c.391+193T>C		intron	N/A	ENSP00000417434.1	B4DFI2
	CLDN11	ENST00000970096.1		c.391+193T>C		intron	N/A	ENSP00000640155.1

Frequencies

GnomAD3 genomes AF: 0.0637 AC: 9685 AN: 152140 Hom.: 736 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0719

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.00471

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0512

GnomAD4 exome AF: 0.0196 AC: 8397 AN: 428666 Hom.: 317 Cov.: 5 AF XY: 0.0186 AC XY: 4136 AN XY: 222724

African (AFR) AF: 0.178 AC: 2200 AN: 12344

American (AMR) AF: 0.0916 AC: 1689 AN: 18440

Ashkenazi Jewish (ASJ) AF: 0.00511 AC: 67 AN: 13124

East Asian (EAS) AF: 0.000229 AC: 7 AN: 30540

South Asian (SAS) AF: 0.0178 AC: 665 AN: 37326

European-Finnish (FIN) AF: 0.00704 AC: 204 AN: 28960

Middle Eastern (MID) AF: 0.0240 AC: 50 AN: 2080

European-Non Finnish (NFE) AF: 0.0108 AC: 2827 AN: 260752

Other (OTH) AF: 0.0274 AC: 688 AN: 25100

GnomAD4 genome AF: 0.0638 AC: 9712 AN: 152258 Hom.: 739 Cov.: 32 AF XY: 0.0627 AC XY: 4667 AN XY: 74454

African (AFR) AF: 0.183 AC: 7603 AN: 41508

American (AMR) AF: 0.0719 AC: 1101 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0139 AC: 67 AN: 4824

European-Finnish (FIN) AF: 0.00471 AC: 50 AN: 10618

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0112 AC: 764 AN: 68034

Other (OTH) AF: 0.0507 AC: 107 AN: 2112

Alfa AF: 0.0217 Hom.: 70

Bravo AF: 0.0759

Asia WGS AF: 0.0240 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.6
DANN	Benign	0.81
PhyloP100		-0.028
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10513681; hg19: chr3-170141308;