Genetic Variant CLDN10:c.*11T>A (chr13-95578025-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006984.5(CLDN10):c.*11T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000441 in 1,361,388 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

CLDN10
NM_006984.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0630

Publications

16 publications found

Variant links:

Genes affected

CLDN10 (HGNC:2033): (claudin 10) 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 expression level of this gene is associated with recurrence of primary hepatocellular carcinoma. Six alternatively spliced transcript variants encoding different isoforms have been reported, but the transcript sequences of some variants are not determined.[provided by RefSeq, Jun 2010]

CLDN10 links:

DZIP1 (HGNC:20908): (DAZ interacting zinc finger protein 1) Predicted to enable metal ion binding activity. Involved in cilium assembly; germ cell development; and spermatogenesis. Located in cytosol; microtubule organizing center; and nucleoplasm. Colocalizes with centriole. Implicated in mitral valve prolapse and spermatogenic failure 47. [provided by Alliance of Genome Resources, Apr 2022]

DZIP1 Gene-Disease associations (from GenCC):

spermatogenic failure 47
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

DZIP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN10	NM_006984.5 link	c.*11T>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000299339.3	NP_008915.1	P78369-1
DZIP1	NM_198968.4 link	c.*4209A>T		downstream_gene_variant		ENST00000376829.7	NP_945319.1	Q86YF9-1B3KSP1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN10	ENST00000299339.3 link	c.*11T>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_006984.5	ENSP00000299339.2		P78369-1
DZIP1	ENST00000376829.7 link	c.*4209A>T		downstream_gene_variant		1	NM_198968.4	ENSP00000366025.2		Q86YF9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000167

AC:

AN:

239476

AF XY:

0.0000232

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:

0.00000928

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000441

AC:

AN:

1361388

Hom.:

Cov.:

AF XY:

0.00000586

AC XY:

AN XY:

682458

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31202

American (AMR)

AF:

0.00

AC:

AN:

43380

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25316

East Asian (EAS)

AF:

0.00

AC:

AN:

39006

South Asian (SAS)

AF:

0.0000603

AC:

AN:

82882

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53066

Middle Eastern (MID)

AF:

0.000180

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1024008

Other (OTH)

AF:

0.00

AC:

AN:

56960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.3

(source)

DANN

Benign

0.77

PhyloP100

-0.063

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over