chr8-8702850-C-T

Variant names:

• chr8-8702850-C-T
• rs372216782
• NM_194284.3:c.452C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_194284.3(CLDN23):​c.452C>T​(p.Pro151Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000723 in 1,604,992 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000073 (0 hom.)
• Consequence: CLDN23 NM_194284.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.14
• Publications: 0 publications found

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]

ENSG00000254367 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194284.3. 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
	CLDN23	NM_194284.3	MANE Select	c.452C>T	p.Pro151Leu	missense	Exon 1 of 1	NP_919260.2	Q96B33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN23	ENST00000519106.2	TSL:6 MANE Select	c.452C>T	p.Pro151Leu	missense	Exon 1 of 1	ENSP00000428780.1	Q96B33
	ENSG00000254367	ENST00000765578.1		n.660+20680G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000785 AC: 18 AN: 229304 AF XY: 0.0000710

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000882

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000148

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000730 AC: 106 AN: 1452816 Hom.: 0 Cov.: 33 AF XY: 0.0000761 AC XY: 55 AN XY: 722484

African (AFR) AF: 0.0000300 AC: 1 AN: 33336

American (AMR) AF: 0.0000674 AC: 3 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25938

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.00 AC: 0 AN: 85794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.0000892 AC: 99 AN: 1109498

Other (OTH) AF: 0.0000499 AC: 3 AN: 60110

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152176 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000869 Hom.: 0

Bravo AF: 0.0000718

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000240 AC: 2

ExAC AF: 0.0000501 AC: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.71	D
M_CAP	Pathogenic	0.77	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.1
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.36
Sift	Benign	0.15	T
Sift4G	Uncertain	0.028	D
Polyphen		0.51	P
Vest4		0.29
MVP		0.86
MPC		0.54
ClinPred		0.61	D
GERP RS		2.3
Varity_R		0.043
gMVP		0.50
Mutation Taster		=94/6	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: rs372216782; hg19: chr8-8560360;