Genetic Variant CLDN34:p.Arg63Cys (chrX-9967544-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001195081.2(CLDN34):c.187C>T(p.Arg63Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000096 in 1,042,183 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict 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. R63G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.6e-7 ( 0 hom. 1 hem. )

Consequence

CLDN34
NM_001195081.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.92

Publications

0 publications found

Variant links:

Genes affected

CLDN34 (HGNC:51259): (claudin 34) Predicted to enable structural molecule activity. Predicted to be involved in bicellular tight junction assembly and cell adhesion. Predicted to be integral component of membrane. Predicted to be active in bicellular tight junction and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CLDN34 links:

ENSG00000310579 (HGNC:):

ENSG00000310579 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11695701).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195081.2. 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
	CLDN34	NM_001195081.2	MANE Select	c.187C>T	p.Arg63Cys	missense	Exon 1 of 1	NP_001182010.1	H7C241

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLDN34	ENST00000445307.4	TSL:6 MANE Select	c.187C>T	p.Arg63Cys	missense	Exon 1 of 1	ENSP00000403980.3	H7C241
ENSG00000310579	ENST00000850985.1		c.4792C>T	p.Arg1598Cys	missense	Exon 10 of 10	ENSP00000521067.1
CLDN34	ENST00000850986.1		c.187C>T	p.Arg63Cys	missense	Exon 2 of 2	ENSP00000521068.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.60e-7

AC:

AN:

1042183

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

341115

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24904

American (AMR)

AF:

0.00

AC:

AN:

27910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18642

East Asian (EAS)

AF:

0.00

AC:

AN:

27131

South Asian (SAS)

AF:

0.00

AC:

AN:

49881

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26032

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4088

European-Non Finnish (NFE)

AF:

0.00000122

AC:

AN:

819291

Other (OTH)

AF:

0.00

AC:

AN:

44304

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.19

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.014

FATHMM_MKL

Benign

0.0074

LIST_S2

Benign

0.41

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

PhyloP100

-1.9

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.012

Sift

Uncertain

0.0040

Sift4G

Benign

0.15

Vest4

0.16

MVP

0.17

ClinPred

0.083

GERP RS

-7.6

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.079

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over