NM_001101389.1:c.178G>A

Variant names:

• chr11-113779973-G-A
• NM_001101389.1:c.178G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001101389.1(CLDN25):​c.178G>A​(p.Val60Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLDN25 NM_001101389.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85
• Publications: 0 publications found

Genes affected

CLDN25 (HGNC:37218): (claudin 25) 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. [provided by RefSeq, Jun 2010]

ACMG classification

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=0.238424).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101389.1. 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
	CLDN25	NM_001101389.1	MANE Select	c.178G>A	p.Val60Ile	missense	Exon 1 of 1	NP_001094859.1	C9JDP6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN25	ENST00000453129.3	TSL:6 MANE Select	c.178G>A	p.Val60Ile	missense	Exon 1 of 1	ENSP00000396304.2	C9JDP6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Benign	0.11
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.049
Eigen_PC	Benign	0.075
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.24	T
MetaSVM	Uncertain	-0.033	T
MutationAssessor	Benign	0.96	L
PhyloP100		3.8
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.28
Sift	Benign	0.043	D
Sift4G	Benign	0.54	T
Polyphen		0.87	P
Vest4		0.057
MutPred		0.56		Gain of ubiquitination at K65 (P = 0.115)
MVP		0.44
MPC		0.020
ClinPred		0.86	D
GERP RS		4.9
PromoterAI		-0.0082	Neutral
Varity_R		0.15
gMVP		0.074
Mutation Taster		=86/14	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

hg19: chr11-113650695;