11-74457366-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

ENSG00000254631 (HGNC:):

ENSG00000254631 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 259778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-74457366-A-G is described in Lovd as [Benign].

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	Q9Y6H6Q6IAE6

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		Q9Y6H6

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

GnomAD3 exomes

AF:

0.132

AC:

33053

AN:

251278

Hom.:

2535

AF XY:

0.136

AC XY:

18476

AN XY:

135816

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 SAS exome

AF:

0.210

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

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.0887

Gnomad4 ASJ exome

AF:

0.107

Gnomad4 EAS exome

AF:

0.147

Gnomad4 SAS exome

AF:

0.208

Gnomad4 FIN exome

AF:

0.218

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.125

AC:

18976

AN:

152250

Hom.:

1316

Cov.:

AF XY:

0.132

AC XY:

9789

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.0903

Gnomad4 ASJ

AF:

0.108

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.228

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.109

Hom.:

2414

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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) -

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

DANN

Benign

0.61

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