17-21702873-C-A

Variant names:

• chr17-21702873-C-A
• rs1207243409
• NM_001194958.2:c.87C>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001194958.2(KCNJ18):​c.87C>A​(p.Asn29Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000871 in 1,594,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: KCNJ18 NM_001194958.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1030654).
• BS2: High AC in GnomAd4 at 65 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ18	NM_001194958.2	c.87C>A	p.Asn29Lys	missense_variant	Exon 3 of 3	ENST00000567955.3	NP_001181887.2
KCNJ18	XM_005276919.4	c.393C>A	p.Asn131Lys	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.87C>A	p.Asn29Lys	missense_variant	Exon 3 of 3	1	NM_001194958.2	ENSP00000457807.2

Frequencies

GnomAD3 genomes AF: 0.000429 AC: 65 AN: 151498 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000483

GnomAD4 exome AF: 0.0000513 AC: 74 AN: 1443352 Hom.: 0 Cov.: 34 AF XY: 0.0000432 AC XY: 31 AN XY: 717774

Gnomad4 AFR exome AF: 0.00157

Gnomad4 AMR exome AF: 0.000183

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000234

GnomAD4 genome AF: 0.000429 AC: 65 AN: 151610 Hom.: 0 Cov.: 34 AF XY: 0.000418 AC XY: 31 AN XY: 74122

Gnomad4 AFR AF: 0.00155

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000478

Bravo AF: 0.000521

ExAC AF: 0.0000577 AC: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	1.6
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.25	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.73	T
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.0	N
Sift	Benign	0.050	D
Sift4G	Benign	0.27	T
Vest4		0.35
MutPred		0.57		Loss of sheet (P = 0.0181);
MVP		0.040
ClinPred		0.20	T
GERP RS		-6.0
Varity_R		0.19
gMVP		0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1207243409; hg19: chr17-21318741;