NM_001185149.1:c.188A>G

Variant names:

• chr4-183322239-T-C
• NM_001185149.1:c.188A>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001185149.1(CLDN24):​c.188A>G​(p.Gln63Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLDN24 NM_001185149.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79
• Publications: 0 publications found

Genes affected

CLDN24 (HGNC:37200): (claudin 24) 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. The protein encoded by this gene is 75% identical to the mouse homolog. This gene is upstream of the CLDN22 gene, which overlaps the WWC2 gene on the opposite strand in the genome.[provided by RefSeq, Aug 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.909

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001185149.1. 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
	CLDN24	NM_001185149.1	MANE Select	c.188A>G	p.Gln63Arg	missense	Exon 1 of 1	NP_001172078.1	A6NM45

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN24	ENST00000541814.1	TSL:6 MANE Select	c.188A>G	p.Gln63Arg	missense	Exon 1 of 1	ENSP00000438400.1	A6NM45

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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	0.29
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.73	D
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Pathogenic	4.1	H
PhyloP100		5.8
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.7	D
REVEL	Pathogenic	0.77
Sift	Benign	0.058	T
Sift4G	Benign	0.14	T
Vest4		0.73
MutPred		0.69		Loss of ubiquitination at K65 (P = 0.1278)
MVP		0.69
MPC		1.4
ClinPred		0.94	D
GERP RS		5.2
PromoterAI		-0.0060	Neutral
Varity_R		0.34
gMVP		0.21
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

hg19: chr4-184243392;