rs368234054

Variant names:

• chr3-190388282-AGG-A
• rs368234054
• NM_006580.4:c.-46_-45delGG

Your query was ambiguous. Multiple possible variants found:

• chr3-190388282-AGG-A
• chr3-190388282-AGG-AG
• chr3-190388282-AGG-AGGG

Variant summary

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

The NM_006580.4(CLDN16):​c.-46_-45delGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 27)
• Consequence: CLDN16 NM_006580.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.808
• Publications: 6 publications found

Genes affected

CLDN16 (HGNC:2037): (claudin 16) Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. It is found primarily in the kidneys, specifically in the thick ascending limb of Henle, where it acts as either an intercellular pore or ion concentration sensor to regulate the paracellular resorption of magnesium ions. Defects in this gene are a cause of primary hypomagnesemia, which is characterized by massive renal magnesium wasting with hypomagnesemia and hypercalciuria, resulting in nephrocalcinosis and renal failure. This gene and the CLDN1 gene are clustered on chromosome 3q28. [provided by RefSeq, Jun 2010]

CLDN16 Gene-Disease associations (from GenCC):

• renal hypomagnesemia 3

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000297357 (HGNC:):

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
CLDN16	NM_006580.4	c.-46_-45delGG		5_prime_UTR_variant	Exon 1 of 5	ENST00000264734.3	NP_006571.2
CLDN16	NM_001378492.1	c.-46_-45delGG		5_prime_UTR_variant	Exon 5 of 9		NP_001365421.1
CLDN16	NM_001378493.1	c.-46_-45delGG		5_prime_UTR_variant	Exon 4 of 8		NP_001365422.1
CLDN16	XM_047447333.1	c.-46_-45delGG		5_prime_UTR_variant	Exon 3 of 7		XP_047303289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN16	ENST00000264734.3	c.-46_-45delGG		5_prime_UTR_variant	Exon 1 of 5	1	NM_006580.4	ENSP00000264734.3
CLDN16	ENST00000456423.2	c.-46_-45delGG		5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000414136.2
ENSG00000297357	ENST00000747317.1	n.267_268delCC		non_coding_transcript_exon_variant	Exon 1 of 2
CLDN16	ENST00000468220.1	n.306+13681_306+13682delGG		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes Cov.: 27

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.81

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

dbSNP: rs368234054; hg19: chr3-190106071;