rs199924386

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_012282.4(KCNE5):c.241T>C(p.Tyr81His) variant causes a missense change. The variant allele was found at a frequency of 0.000254 in 1,211,196 control chromosomes in the GnomAD database, including 2 homozygotes. There are 106 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., 19 hem., cov: 25)

Exomes 𝑓: 0.00025 ( 2 hom. 87 hem. )

Consequence

KCNE5
NM_012282.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 5.73

Variant links:

Genes affected

KCNE5 (HGNC:6241): (potassium voltage-gated channel subfamily E regulatory subunit 5) This gene encodes a member of a family of single pass transmembrane domain proteins that function as ancillary subunits to voltage-gated potassium channels. Members of this family affect diverse processes in potassium channel regulation, including ion selectivity, voltage dependence, and anterograde recycling from the plasma membrane. Variants of this gene are associated with idiopathic ventricular fibrillation and Brugada syndrome. [provided by RefSeq, Nov 2016]

KCNE5 links:

ACSL4 (HGNC:3571): (acyl-CoA synthetase long chain family member 4) The protein encoded by this gene is an isozyme of the long-chain fatty-acid-coenzyme A ligase family. Although differing in substrate specificity, subcellular localization, and tissue distribution, all isozymes of this family convert free long-chain fatty acids into fatty acyl-CoA esters, and thereby play a key role in lipid biosynthesis and fatty acid degradation. This isozyme preferentially utilizes arachidonate as substrate. The absence of this enzyme may contribute to the cognitive disability or Alport syndrome. Alternative splicing of this gene generates multiple transcript variants. [provided by RefSeq, Jan 2016]

ACSL4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008243412).

BP6

Variant X-109624780-A-G is Benign according to our data. Variant chrX-109624780-A-G is described in ClinVar as [Benign]. Clinvar id is 463280.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-109624780-A-G is described in Lovd as [Benign].

BS2

High Hemizygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNE5	NM_012282.4 link	c.241T>C	p.Tyr81His	missense_variant	Exon 1 of 1	ENST00000372101.3	NP_036414.1	Q9UJ90

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE5	ENST00000372101.3 link	c.241T>C	p.Tyr81His	missense_variant	Exon 1 of 1	6	NM_012282.4	ENSP00000361173.2		Q9UJ90
ACSL4	ENST00000439581.1 link	n.387-459T>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

113280

Hom.:

Cov.:

AF XY:

0.000536

AC XY:

AN XY:

35448

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:

0.00874

Gnomad SAS

AF:

0.000703

Gnomad FIN

AF:

0.000158

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000560

AC:

101

AN:

180382

Hom.:

AF XY:

0.000498

AC XY:

AN XY:

66224

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00705

Gnomad SAS exome

AF:

0.000158

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000448

GnomAD4 exome

AF:

0.000249

AC:

273

AN:

1097871

Hom.:

Cov.:

AF XY:

0.000239

AC XY:

AN XY:

363345

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00775

Gnomad4 SAS exome

AF:

0.0000554

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000594

Gnomad4 OTH exome

AF:

0.000673

GnomAD4 genome

AF:

0.000309

AC:

AN:

113325

Hom.:

Cov.:

AF XY:

0.000535

AC XY:

AN XY:

35503

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00877

Gnomad4 SAS

AF:

0.000705

Gnomad4 FIN

AF:

0.000158

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000485

Hom.:

Bravo

AF:

0.000223

ExAC

AF:

0.000602

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Brugada syndrome

Benign:1

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

KCNE5-related disorder

Benign:1

Feb 15, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.86

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.0082

MetaSVM

Uncertain

-0.23

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-4.8

REVEL

Uncertain

0.59

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

0.062

Vest4

0.27

MVP

0.19

MPC

1.4

ClinPred

0.15

GERP RS

3.5

Varity_R

0.90

gMVP

0.92

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