Variant 8-8702666-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_194284.3(CLDN23):c.268G>A(p.Ala90Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00494 in 1,604,364 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0050 ( 34 hom. )

Consequence

CLDN23
NM_194284.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.385

Variant links:

Genes affected

CLDN23 (HGNC:17591): (claudin 23) 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. This gene is expressed in germinal center B-cells, placenta and stomach as well as in colon tumor. This gene is down-regulated in intestinal type gastric cancer. [provided by RefSeq, Aug 2010]

CLDN23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032530725).

BP6

Variant 8-8702666-G-A is Benign according to our data. Variant chr8-8702666-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658375.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDN23	NM_194284.3 linkuse as main transcript	c.268G>A	p.Ala90Thr	missense_variant	1/1	ENST00000519106.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN23	ENST00000519106.2 linkuse as main transcript	c.268G>A	p.Ala90Thr	missense_variant	1/1		NM_194284.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00419

AC:

637

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00477

Gnomad ASJ

AF:

0.0265

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00523

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00483

AC:

1093

AN:

226404

Hom.:

AF XY:

0.00512

AC XY:

639

AN XY:

124872

show subpopulations

Gnomad AFR exome

AF:

0.000887

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.0238

Gnomad EAS exome

AF:

0.0000580

Gnomad SAS exome

AF:

0.00615

Gnomad FIN exome

AF:

0.00185

Gnomad NFE exome

AF:

0.00470

Gnomad OTH exome

AF:

0.00532

GnomAD4 exome

AF:

0.00502

AC:

7285

AN:

1452050

Hom.:

Cov.:

AF XY:

0.00518

AC XY:

3739

AN XY:

722194

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00484

Gnomad4 ASJ exome

AF:

0.0243

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00634

Gnomad4 FIN exome

AF:

0.00117

Gnomad4 NFE exome

AF:

0.00482

Gnomad4 OTH exome

AF:

0.00641

GnomAD4 genome

AF:

0.00418

AC:

637

AN:

152314

Hom.:

Cov.:

AF XY:

0.00442

AC XY:

329

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.0265

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00684

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00523

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00631

Hom.:

Bravo

AF:

0.00415

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.000930

AC:

ESP6500EA

AF:

0.00650

AC:

ExAC

AF:

0.00438

AC:

526

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

CLDN23: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

Cadd

Benign

0.49

Dann

Benign

0.94

DEOGEN2

Benign

0.17

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.060

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.79

MutationAssessor

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

0.050

REVEL

Benign

0.16

Sift

Benign

0.37

Sift4G

Benign

0.41

Polyphen

0.0010

Vest4

0.047

MVP

0.52

MPC

0.18

ClinPred

0.0015

GERP RS

-6.9

Varity_R

0.031

gMVP

0.56

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