chr14-90184170-C-T

Variant names:

• chr14-90184170-C-T
• rs55730840
• NM_022054.4:c.394C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_022054.4(KCNK13):​c.394C>T​(p.Leu132Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00648 in 1,614,220 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0056 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0066 (41 hom.)
• Consequence: KCNK13 NM_022054.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.13
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018620014).
• BP6: Variant 14-90184170-C-T is Benign according to our data. Variant chr14-90184170-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2644447.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022054.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK13	NM_022054.4	MANE Select	c.394C>T	p.Leu132Phe	missense	Exon 2 of 2	NP_071337.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK13	ENST00000282146.5	TSL:1 MANE Select	c.394C>T	p.Leu132Phe	missense	Exon 2 of 2	ENSP00000282146.4	Q9HB14
	KCNK13	ENST00000954166.1		c.439C>T	p.Leu147Phe	missense	Exon 3 of 3	ENSP00000624225.1

Frequencies

GnomAD3 genomes AF: 0.00556 AC: 847 AN: 152226 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00817

Gnomad OTH AF: 0.00907

GnomAD2 exomes AF: 0.00406 AC: 1022 AN: 251424 AF XY: 0.00401

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00552

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000832

Gnomad NFE exome AF: 0.00664

Gnomad OTH exome AF: 0.00636

GnomAD4 exome AF: 0.00658 AC: 9612 AN: 1461876 Hom.: 41 Cov.: 32 AF XY: 0.00637 AC XY: 4631 AN XY: 727240

African (AFR) AF: 0.00111 AC: 37 AN: 33480

American (AMR) AF: 0.00570 AC: 255 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00114 AC: 61 AN: 53416

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.00797 AC: 8868 AN: 1111998

Other (OTH) AF: 0.00624 AC: 377 AN: 60396

GnomAD4 genome AF: 0.00555 AC: 846 AN: 152344 Hom.: 6 Cov.: 33 AF XY: 0.00546 AC XY: 407 AN XY: 74498

African (AFR) AF: 0.00144 AC: 60 AN: 41578

American (AMR) AF: 0.0118 AC: 181 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000942 AC: 10 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00816 AC: 555 AN: 68036

Other (OTH) AF: 0.00898 AC: 19 AN: 2116

Alfa AF: 0.00625 Hom.: 6

Bravo AF: 0.00552

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00623 AC: 24

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00849 AC: 73

ExAC AF: 0.00378 AC: 459

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00889

EpiControl AF: 0.00747

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Uncertain	0.010
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		6.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.32
Sift	Benign	0.32	T
Sift4G	Benign	0.30	T
Polyphen		0.74	P
Vest4		0.88
MVP		0.68
MPC		0.65
ClinPred		0.055	T
GERP RS		5.3
Varity_R		0.14
gMVP		0.88
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs55730840; hg19: chr14-90650514;