rs557940021

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004823.3(KCNK6):c.149G>A(p.Arg50His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000501 in 1,558,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

KCNK6
NM_004823.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67

Publications

0 publications found

Variant links:

Genes affected

KCNK6 (HGNC:6281): (potassium two pore domain channel subfamily K member 6) This gene encodes one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. This channel protein, considered an open rectifier, is widely expressed. It is stimulated by arachidonic acid, and inhibited by internal acidification and volatile anaesthetics. [provided by RefSeq, Jul 2008]

KCNK6 links:

YIF1B (HGNC:30511): (Yip1 interacting factor homolog B, membrane trafficking protein) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport; protein targeting to membrane; and sperm axoneme assembly. Located in Golgi apparatus; endoplasmic reticulum; and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]

YIF1B Gene-Disease associations (from GenCC):

Kaya-Barakat-Masson syndrome
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

YIF1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.021065414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK6	NM_004823.3 link	c.149G>A	p.Arg50His	missense_variant	Exon 1 of 3	ENST00000263372.5	NP_004814.1	Q9Y257-1B2RDS2
YIF1B	XM_047439648.1 link	c.-36+1729C>T		intron_variant	Intron 1 of 7		XP_047295604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK6	ENST00000263372.5 link	c.149G>A	p.Arg50His	missense_variant	Exon 1 of 3	1	NM_004823.3	ENSP00000263372.2		Q9Y257-1
KCNK6	ENST00000588137.1 link	n.-144G>A		upstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000652

AC:

AN:

168730

AF XY:

0.0000530

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000181

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000684

Gnomad OTH exome

AF:

0.000219

GnomAD4 exome

AF:

0.0000491

AC:

AN:

1405946

Hom.:

Cov.:

AF XY:

0.0000416

AC XY:

AN XY:

697014

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31450

American (AMR)

AF:

0.000182

AC:

AN:

38554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25082

East Asian (EAS)

AF:

0.00

AC:

AN:

36532

South Asian (SAS)

AF:

0.00

AC:

AN:

82262

European-Finnish (FIN)

AF:

0.0000274

AC:

AN:

36456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5178

European-Non Finnish (NFE)

AF:

0.0000485

AC:

AN:

1091948

Other (OTH)

AF:

0.000137

AC:

AN:

58484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41592

American (AMR)

AF:

0.000196

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000175

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.0000348

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 08, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.149G>A (p.R50H) alteration is located in exon 1 (coding exon 1) of the KCNK6 gene. This alteration results from a G to A substitution at nucleotide position 149, causing the arginine (R) at amino acid position 50 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.61

M_CAP

Benign

0.018

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

1.7

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.37

REVEL

Benign

0.016

Sift

Benign

0.15

Sift4G

Benign

0.18

Polyphen

0.031

Vest4

0.085

MutPred

0.41

Gain of loop (P = 0.0195);

MVP

0.24

MPC

1.6

ClinPred

0.037

GERP RS

-0.11

PromoterAI

0.011

Neutral

(source)

Varity_R

0.034

gMVP

0.32

Mutation Taster

=95/5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over