rs375663820

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_006984.5(CLDN10):c.271T>C(p.Phe91Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CLDN10
NM_006984.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.85

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a chain Claudin-10 (size 227) in uniprot entity CLD10_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_006984.5

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN10	NM_006984.5 link	c.271T>C	p.Phe91Leu	missense_variant	Exon 2 of 5	ENST00000299339.3	NP_008915.1	P78369-1
CLDN10	NM_182848.4 link	c.265T>C	p.Phe89Leu	missense_variant	Exon 2 of 5		NP_878268.1	P78369-2
CLDN10	NM_001160100.2 link	c.208T>C	p.Phe70Leu	missense_variant	Exon 2 of 5		NP_001153572.1	P78369-3
CLDN10	XM_047430765.1 link	c.97T>C	p.Phe33Leu	missense_variant	Exon 3 of 6		XP_047286721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CLDN10	ENST00000299339.3 link	c.271T>C	p.Phe91Leu	missense_variant	Exon 2 of 5	1	NM_006984.5	ENSP00000299339.2	P78369-1
CLDN10	ENST00000376873.7 link	c.265T>C	p.Phe89Leu	missense_variant	Exon 2 of 5	2		ENSP00000366069.2	P78369-2
CLDN10	ENST00000376855.1 link	c.25T>C	p.Phe9Leu	missense_variant	Exon 1 of 2	2		ENSP00000366051.1	Q5W075

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Jul 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.271T>C (p.F91L) alteration is located in exon 2 (coding exon 2) of the CLDN10 gene. This alteration results from a T to C substitution at nucleotide position 271, causing the phenylalanine (F) at amino acid position 91 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.69

.;D;D

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.86

D;D;D

M_CAP

Benign

0.053

MetaRNN

Uncertain

0.68

D;D;D

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

1.5

.;L;.

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Pathogenic

0.77

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.99

.;D;.

Vest4

0.61

MutPred

0.62

.;Gain of catalytic residue at F96 (P = 0);.;

MVP

0.93

MPC

0.78

ClinPred

0.98

GERP RS

5.8

Varity_R

0.42

gMVP

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over