chr17-21703150-C-A

Variant names:

• chr17-21703150-C-A
• rs1369395713
• NM_001194958.2:c.364C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001194958.2(KCNJ18):​c.364C>A​(p.Pro122Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 37)
• Consequence: KCNJ18 NM_001194958.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ18	NM_001194958.2	c.364C>A	p.Pro122Thr	missense_variant	Exon 3 of 3	ENST00000567955.3	NP_001181887.2
KCNJ18	XM_005276919.4	c.670C>A	p.Pro224Thr	missense_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.364C>A	p.Pro122Thr	missense_variant	Exon 3 of 3	1	NM_001194958.2	ENSP00000457807.2

Frequencies

GnomAD3 genomes Cov.: 37

GnomAD4 exome Cov.: 141

GnomAD4 genome Cov.: 37

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.46
CADD	Benign	23
DEOGEN2	Uncertain	0.71	D
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Pathogenic	0.94	D
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-6.6	D
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.018	D
Vest4		0.29
MutPred		0.80		Loss of phosphorylation at T121 (P = 0.0652);
MVP		0.31
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.69
gMVP		0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1369395713; hg19: chr17-21319018;