11-74457366-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005472.5(KCNE3):c.198T>C(p.Phe66Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,614,094 control chromosomes in the GnomAD database, including 12,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1316 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11444 hom. )

Consequence

KCNE3
NM_005472.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.433

Publications

26 publications found

Variant links:

Genes affected

KCNE3 (HGNC:6243): (potassium voltage-gated channel subfamily E regulatory subunit 3) Voltage-gated potassium (Kv) 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 member of the potassium channel, voltage-gated, isk-related subfamily. This member is a type I membrane protein, and a beta subunit that assembles with a potassium channel alpha-subunit to modulate the gating kinetics and enhance stability of the multimeric complex. This gene is prominently expressed in the kidney. A missense mutation in this gene is associated with hypokalemic periodic paralysis. [provided by RefSeq, Jul 2008]

KCNE3 Gene-Disease associations (from GenCC):

Brugada syndrome 6
Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Genomics England PanelApp, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
Brugada syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

KCNE3 links:

ENSG00000254928 (HGNC:):

ENSG00000254928 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 11-74457366-A-G is Benign according to our data. Variant chr11-74457366-A-G is described in ClinVar as Benign. ClinVar VariationId is 259778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.433 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNE3	NM_005472.5 link	c.198T>C	p.Phe66Phe	synonymous_variant	Exon 3 of 3	ENST00000310128.9	NP_005463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE3	ENST00000310128.9 link	c.198T>C	p.Phe66Phe	synonymous_variant	Exon 3 of 3	1	NM_005472.5	ENSP00000310557.4

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

18972

AN:

152132

Hom.:

1316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.0907

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.103

GnomAD2 exomes

AF:

0.132

AC:

33053

AN:

251278

AF XY:

0.136

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.0873

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.130

Gnomad FIN exome

AF:

0.219

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.120

AC:

175488

AN:

1461844

Hom.:

11444

Cov.:

AF XY:

0.123

AC XY:

89420

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.126

AC:

4204

AN:

33478

American (AMR)

AF:

0.0887

AC:

3965

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

2806

AN:

26132

East Asian (EAS)

AF:

0.147

AC:

5818

AN:

39698

South Asian (SAS)

AF:

0.208

AC:

17913

AN:

86258

European-Finnish (FIN)

AF:

0.218

AC:

11654

AN:

53416

Middle Eastern (MID)

AF:

0.121

AC:

699

AN:

5768

European-Non Finnish (NFE)

AF:

0.109

AC:

120899

AN:

1111978

Other (OTH)

AF:

0.125

AC:

7530

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

8998

17995

26993

35990

44988

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4498

8996

13494

17992

22490

<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:

0.125

AC:

18976

AN:

152250

Hom.:

1316

Cov.:

AF XY:

0.132

AC XY:

9789

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.123

AC:

5111

AN:

41558

American (AMR)

AF:

0.0903

AC:

1383

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

375

AN:

3472

East Asian (EAS)

AF:

0.144

AC:

747

AN:

5186

South Asian (SAS)

AF:

0.208

AC:

1004

AN:

4824

European-Finnish (FIN)

AF:

0.228

AC:

2409

AN:

10586

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.111

AC:

7533

AN:

68000

Other (OTH)

AF:

0.102

AC:

216

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

868

1735

2603

3470

4338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.112

Hom.:

4926

Bravo

AF:

0.111

Asia WGS

AF:

0.187

AC:

653

AN:

3478

EpiCase

AF:

0.106

EpiControl

AF:

0.106

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 10, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 16374062) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Brugada syndrome 6

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

May 14, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.61

PhyloP100

0.43

Mutation Taster

=98/2

polymorphism (auto)

(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