X-9967920-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001195081.2(CLDN34):​c.563C>T​(p.Pro188Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,040,484 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 0.000011 ( 0 hom. 6 hem. )

Consequence

CLDN34
NM_001195081.2 missense

Scores

12

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.17
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.071321934).
BP6
Variant X-9967920-C-T is Benign according to our data. Variant chrX-9967920-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3493429.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLDN34NM_001195081.2 linkc.563C>T p.Pro188Leu missense_variant Exon 1 of 1 ENST00000445307.4 NP_001182010.1 H7C241

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLDN34ENST00000445307.4 linkc.563C>T p.Pro188Leu missense_variant Exon 1 of 1 6 NM_001195081.2 ENSP00000403980.3 H7C241

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
AF:
0.0000106
AC:
11
AN:
1040484
Hom.:
0
Cov.:
30
AF XY:
0.0000177
AC XY:
6
AN XY:
339560
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000369
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000122
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
22
Bravo
AF:
0.00000756

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Dec 10, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.94
CADD
Benign
0.035
DANN
Benign
0.21
DEOGEN2
Benign
0.0039
T
FATHMM_MKL
Benign
0.00052
N
LIST_S2
Benign
0.32
T
MetaRNN
Benign
0.071
T
MetaSVM
Benign
-0.95
T
PrimateAI
Benign
0.19
T
REVEL
Benign
0.072
Sift4G
Benign
1.0
T
Vest4
0.094
MVP
0.21
ClinPred
0.022
T
GERP RS
1.0
Varity_R
0.051
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs2084913091; hg19: chrX-9935960; API