rs757369739

Variant names:

• chr4-183322024-C-A
• rs757369739
• NM_001185149.1:c.403G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-183322024-C-A
• chr4-183322024-C-G

Variant summary

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

The NM_001185149.1(CLDN24):​c.403G>T​(p.Val135Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,556 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V135L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CLDN24 NM_001185149.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.728
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN24	NM_001185149.1	c.403G>T	p.Val135Phe	missense_variant	Exon 1 of 1	ENST00000541814.1	NP_001172078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN24	ENST00000541814.1	c.403G>T	p.Val135Phe	missense_variant	Exon 1 of 1	6	NM_001185149.1	ENSP00000438400.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461556 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727066

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111794

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Uncertain	0.70	D
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.73
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.62
Sift	Benign	0.23	T
Sift4G	Benign	0.16	T
Vest4		0.41
MutPred		0.65		Loss of stability (P = 0.0979);
MVP		0.69
MPC		0.97
ClinPred		0.27	T
GERP RS		2.0
PromoterAI		0.044	Neutral
Varity_R		0.15
gMVP		0.72
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs757369739; hg19: chr4-184243177;