7-90413211-ATT-GTG

Variant names:

• chr7-90413211-ATT-GTG
• NM_001185072.3:c.535_537delATTinsGTG
• CLDN12 p.Ile179Val

Variant summary

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

The NM_001185072.3(CLDN12):​c.535_537delATTinsGTG​(p.Ile179Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLDN12 NM_001185072.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.77
• Publications: 0 publications found

Genes affected

CLDN12 (HGNC:2034): (claudin 12) 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. This gene is expressed in the inner ear and bladder epithelium, and it is over-expressed in colorectal carcinomas. This protein and claudin 2 are critical for vitamin D-dependent Ca2+ absorption between enterocytes. Multiple alternatively spliced transcript variants encoding the same protein have been found.[provided by RefSeq, Sep 2011]

ENSG00000273299 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001185072.3. 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
	CLDN12	NM_001185072.3	MANE Select	c.535_537delATTinsGTG	p.Ile179Val	missense	N/A	NP_001172001.1	P56749
	CLDN12	NM_001185073.3		c.535_537delATTinsGTG	p.Ile179Val	missense	N/A	NP_001172002.1	P56749
	CLDN12	NM_012129.5		c.535_537delATTinsGTG	p.Ile179Val	missense	N/A	NP_036261.1	P56749

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN12	ENST00000496677.6	TSL:1 MANE Select	c.535_537delATTinsGTG	p.Ile179Val	missense	N/A	ENSP00000419053.1	P56749
	CLDN12	ENST00000287916.8	TSL:1	c.535_537delATTinsGTG	p.Ile179Val	missense	N/A	ENSP00000287916.4	P56749
	CLDN12	ENST00000394605.2	TSL:2	c.535_537delATTinsGTG	p.Ile179Val	missense	N/A	ENSP00000378103.1	P56749

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-90042525;