rs1485559223

Variant names:

• chr14-90062392-G-A
• NM_022054.4:c.187G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-90062392-G-A
• chr14-90062392-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022054.4(KCNK13):​c.187G>A​(p.Gly63Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000644 in 1,396,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: KCNK13 NM_022054.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

Genes affected

KCNK13 (HGNC:6275): (potassium two pore domain channel subfamily K member 13) Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a potassium channel containing two pore-forming domains. This protein is an open channel that can be stimulated by arachidonic acid and inhibited by the anesthetic halothane. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027609318).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK13	NM_022054.4	c.187G>A	p.Gly63Ser	missense_variant	Exon 1 of 2	ENST00000282146.5	NP_071337.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK13	ENST00000282146.5	c.187G>A	p.Gly63Ser	missense_variant	Exon 1 of 2	1	NM_022054.4	ENSP00000282146.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000644 AC: 9 AN: 1396532 Hom.: 0 Cov.: 35 AF XY: 0.00000290 AC XY: 2 AN XY: 688662

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000741

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.20	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.75	N
REVEL	Benign	0.017
Sift	Benign	0.76	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.073
MutPred		0.47		Gain of catalytic residue at L66 (P = 2e-04);
MVP		0.17
MPC		1.1
ClinPred		0.043	T
GERP RS		-5.7
Varity_R		0.035
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-90528736; COSMIC: COSV56411835;