Genetic Variant NM_022054.4:c.155G>A (chr14-90062360-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022054.4(KCNK13):c.155G>A(p.Arg52His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R52P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNK13
NM_022054.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.60

Publications

0 publications found

Variant links:

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]

KCNK13 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24536705).

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.155G>A	p.Arg52His	missense	Exon 1 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.155G>A	p.Arg52His	missense	Exon 1 of 2	ENSP00000282146.4	Q9HB14
	KCNK13	ENST00000954166.1		c.155G>A	p.Arg52His	missense	Exon 1 of 3	ENSP00000624225.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

155802

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1403712

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693418

African (AFR)

AF:

0.00

AC:

AN:

31666

American (AMR)

AF:

0.00

AC:

AN:

37030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25116

East Asian (EAS)

AF:

0.00

AC:

AN:

36404

South Asian (SAS)

AF:

0.00

AC:

AN:

79860

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4710

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1084492

Other (OTH)

AF:

0.00

AC:

AN:

58044

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000891

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.80

M_CAP

Benign

0.054

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

2.6

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.4

REVEL

Benign

0.11

Sift

Benign

0.49

Sift4G

Benign

0.20

Polyphen

0.97

Vest4

0.062

MutPred

0.54

Loss of MoRF binding (P = 0.0133)

MVP

0.45

MPC

2.1

ClinPred

0.93

GERP RS

3.3

PromoterAI

0.020

Neutral

(source)

Varity_R

0.13

gMVP

0.68

Mutation Taster

=66/34

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over