chr8-8702573-C-T

Variant names:

• chr8-8702573-C-T
• rs369577087
• NM_194284.3:c.175C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_194284.3(CLDN23):​c.175C>T​(p.Arg59Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,610,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R59H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: CLDN23 NM_194284.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00100
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.32237956).

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.175C>T	p.Arg59Cys	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.175C>T	p.Arg59Cys	missense	Exon 1 of 1	ENSP00000428780.1	Q96B33
	ENSG00000254367	ENST00000765578.1		n.660+20957G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152192 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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

GnomAD2 exomes AF: 0.0000212 AC: 5 AN: 236256 AF XY: 0.0000232

Gnomad AFR exome AF: 0.000142

Gnomad AMR exome AF: 0.0000294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000955

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1457780 Hom.: 0 Cov.: 33 AF XY: 0.0000152 AC XY: 11 AN XY: 724830

African (AFR) AF: 0.000479 AC: 16 AN: 33374

American (AMR) AF: 0.0000674 AC: 3 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26000

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110180

Other (OTH) AF: 0.0000832 AC: 5 AN: 60132

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152310 Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7 AN XY: 74464

African (AFR) AF: 0.000313 AC: 13 AN: 41584

American (AMR) AF: 0.000327 AC: 5 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000162

ESP6500AA AF: 0.000242 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000414 AC: 5

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	Pathogenic	0.58
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.24	N
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.052	D
MutationAssessor	Benign	1.7	L
PhyloP100		-0.0010
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.40
Sift	Benign	0.092	T
Sift4G	Benign	0.18	T
Polyphen		0.97	D
Vest4		0.27
MVP		0.77
MPC		0.68
ClinPred		0.11	T
GERP RS		-0.89
Varity_R		0.067
gMVP		0.57
Mutation Taster		=95/5	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: rs369577087; hg19: chr8-8560083;