Variant chr6-39314100-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_031460.4(KCNK17):c.221T>A(p.Leu74Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000082 in 1,585,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

KCNK17
NM_031460.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.34

Variant links:

Genes affected

KCNK17 (HGNC:14465): (potassium two pore domain channel subfamily K member 17) The protein encoded by this gene belongs to the family of potassium channel proteins containing two pore-forming P domains. This channel is an open rectifier which primarily passes outward current under physiological K+ concentrations. This gene is activated at alkaline pH. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

KCNK17 links:

LOC105375047 (HGNC:):

LOC105375047 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KCNK17	NM_031460.4 linkuse as main transcript	c.221T>A	p.Leu74Gln	missense_variant	1/5	ENST00000373231.9	NP_113648.2
LOC105375047	XR_926774.3 linkuse as main transcript	n.145A>T		non_coding_transcript_exon_variant	1/3
KCNK17	NM_001135111.2 linkuse as main transcript	c.221T>A	p.Leu74Gln	missense_variant	1/6		NP_001128583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK17	ENST00000373231.9 linkuse as main transcript	c.221T>A	p.Leu74Gln	missense_variant	1/5	1	NM_031460.4	ENSP00000362328	P1	Q96T54-3
KCNK17	ENST00000503878.1 linkuse as main transcript	n.326T>A		non_coding_transcript_exon_variant	1/3	1
KCNK17	ENST00000453413.2 linkuse as main transcript	c.221T>A	p.Leu74Gln	missense_variant	1/6	5		ENSP00000401271		Q96T54-4

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000190

AC:

AN:

210620

Hom.:

AF XY:

0.0000172

AC XY:

AN XY:

116526

show subpopulations

Gnomad AFR exome

AF:

0.0000850

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000837

AC:

AN:

1433412

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

710430

show subpopulations

Gnomad4 AFR exome

AF:

0.0000621

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152000

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

Asia WGS

AF:

0.000289

AC:

AN:

3474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.221T>A (p.L74Q) alteration is located in exon 1 (coding exon 1) of the KCNK17 gene. This alteration results from a T to A substitution at nucleotide position 221, causing the leucine (L) at amino acid position 74 to be replaced by a glutamine (Q). 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

Pathogenic

0.70

BayesDel_addAF

Uncertain

0.076

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.023

MetaRNN

Pathogenic

0.86

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.3

M;M

MutationTaster

Benign

0.97

D;D

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.0

D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.029

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.99

D;.

Vest4

0.82

MutPred

0.66

Loss of stability (P = 0.0189);Loss of stability (P = 0.0189);

MVP

0.56

MPC

0.65

ClinPred

0.95

GERP RS

4.3

Varity_R

0.61

gMVP

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over