Variant chr17-21703441-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001194958.2(KCNJ18):c.655C>T(p.Arg219Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000381 in 152,418 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 53)

Exomes 𝑓: 0.00046 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNJ18
NM_001194958.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0120

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 58 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ18	NM_001194958.2 linkuse as main transcript	c.655C>T	p.Arg219Cys	missense_variant	3/3	ENST00000567955.3	NP_001181887.2
KCNJ18	XM_005276919.4 linkuse as main transcript	c.961C>T	p.Arg321Cys	missense_variant	2/2		XP_005276976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ18	ENST00000567955.3 linkuse as main transcript	c.655C>T	p.Arg219Cys	missense_variant	3/3	1	NM_001194958.2	ENSP00000457807	P1

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152300

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000964

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.000955

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000465

AC:

679

AN:

1460696

Hom.:

Cov.:

220

AF XY:

0.000469

AC XY:

341

AN XY:

726664

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.000962

Gnomad4 ASJ exome

AF:

0.000880

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.000428

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.000381

AC:

AN:

152418

Hom.:

Cov.:

AF XY:

0.000429

AC XY:

AN XY:

74540

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.000945

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000346

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Thyrotoxic periodic paralysis, susceptibility to, 2

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues

Apr 24, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.51

BayesDel_noAF

Pathogenic

0.50

CADD

Pathogenic

DEOGEN2

Pathogenic

0.88

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.86

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.35

MetaRNN

Uncertain

0.71

MetaSVM

Pathogenic

1.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.93

PROVEAN

Pathogenic

-7.7

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.57

MVP

0.48

ClinPred

0.78

GERP RS

3.2

Varity_R

0.89

gMVP

0.76

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over