Variant 11-64293042-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_033310.3(KCNK4):c.24C>T(p.Ala8=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00637 in 1,547,802 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0066 ( 46 hom. )

Consequence

KCNK4
NM_033310.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -6.10

Variant links:

Genes affected

KCNK4 (HGNC:6279): (potassium two pore domain channel subfamily K member 4) This gene encodes a member of the TWIK-related arachidonic acid-stimulated two pore potassium channel subfamily. The encoded protein homodimerizes and functions as an outwardly rectifying channel. This channel is regulated by polyunsaturated fatty acids, temperature and mechanical deformation of the lipid membrane. This protein is expressed primarily in neural tissues and may be involved in regulating the noxious input threshold in dorsal root ganglia neurons. Alternate splicing results in multiple transcript variants. Naturally occurring read-through transcripts also exist between this gene and the downstream testis expressed 40 (TEX40) gene, as represented in GeneID: 106780802. [provided by RefSeq, Nov 2015]

KCNK4 links:

KCNK4-CATSPERZ (HGNC:):

KCNK4-CATSPERZ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 11-64293042-C-T is Benign according to our data. Variant chr11-64293042-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1575952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.1 with no splicing effect.

BS2

High AC in GnomAd4 at 594 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK4	NM_033310.3 linkuse as main transcript	c.24C>T	p.Ala8=	synonymous_variant	2/7	ENST00000422670.7	NP_201567.1
KCNK4-CATSPERZ	NR_133662.1 linkuse as main transcript	n.165C>T		non_coding_transcript_exon_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK4	ENST00000422670.7 linkuse as main transcript	c.24C>T	p.Ala8=	synonymous_variant	2/7	1	NM_033310.3	ENSP00000402797	P2	Q9NYG8-1

Frequencies

GnomAD3 genomes

AF:

0.00390

AC:

594

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00307

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00660

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00345

AC:

522

AN:

151356

Hom.:

AF XY:

0.00349

AC XY:

279

AN XY:

79890

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.00201

Gnomad ASJ exome

AF:

0.00356

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000716

Gnomad FIN exome

AF:

0.00185

Gnomad NFE exome

AF:

0.00661

Gnomad OTH exome

AF:

0.00234

GnomAD4 exome

AF:

0.00664

AC:

9260

AN:

1395438

Hom.:

Cov.:

AF XY:

0.00636

AC XY:

4377

AN XY:

688208

show subpopulations

Gnomad4 AFR exome

AF:

0.000827

Gnomad4 AMR exome

AF:

0.00189

Gnomad4 ASJ exome

AF:

0.00287

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000939

Gnomad4 FIN exome

AF:

0.00177

Gnomad4 NFE exome

AF:

0.00797

Gnomad4 OTH exome

AF:

0.00586

GnomAD4 genome

AF:

0.00390

AC:

594

AN:

152364

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

262

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00660

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00510

Hom.:

Bravo

AF:

0.00386

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	KCNK4-TEX40: BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

KCNK4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 06, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.0

DANN

Benign

0.94

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