rs527236153

Variant names:

• chr17-21703213-AC-A
• rs527236153
• NM_001194958.2:c.429delC

Variant summary

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

The NM_001194958.2(KCNJ18):​c.429delC​(p.Ile144SerfsTer8) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: not found (cov: 36)
• Consequence: KCNJ18 NM_001194958.2 frameshift
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 6.58
• Publications: 2 publications found

Genes affected

KCNJ18 (HGNC:39080): (potassium inwardly rectifying channel subfamily J member 18) This gene encodes a member of the inwardly rectifying potassium channel family. Transcription of this locus is regulated by thyroid hormone, and the encoded protein plays a role in resting membrane potential maintenance. Mutations in this locus have been associated with thyrotoxic hypokalemic periodic paralysis. [provided by RefSeq, Jan 2013]

KCNJ18 Gene-Disease associations (from GenCC):

• thyrotoxic periodic paralysis, susceptibility to, 2

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics

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
KCNJ18	NM_001194958.2	c.429delC	p.Ile144SerfsTer8	frameshift_variant	Exon 3 of 3	ENST00000567955.3	NP_001181887.2
KCNJ18	XM_005276919.4	c.735delC	p.Ile246SerfsTer8	frameshift_variant	Exon 2 of 2		XP_005276976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ18	ENST00000567955.3	c.429delC	p.Ile144SerfsTer8	frameshift_variant	Exon 3 of 3	1	NM_001194958.2	ENSP00000457807.2

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Cov.: 128

GnomAD4 genome Cov.: 36

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Thyrotoxic periodic paralysis, susceptibility to, 2 Other:1

Jan 08, 2010

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.6

Splicing

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

Other links and lift over

dbSNP: rs527236153; hg19: chr17-21319081;