rs763754260

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000219.6(KCNE1):c.123G>C(p.Lys41Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K41M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 13)

Exomes 𝑓: 0.0000083 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

KCNE1
NM_000219.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.625

Publications

2 publications found

Variant links:

Genes affected

KCNE1 (HGNC:6240): (potassium voltage-gated channel subfamily E regulatory subunit 1) The product of this gene belongs to the potassium channel KCNE family. Potassium ion channels are essential to many cellular functions and show a high degree of diversity, varying in their electrophysiologic and pharmacologic properties. This gene encodes a transmembrane protein known to associate with the product of the KVLQT1 gene to form the delayed rectifier potassium channel. Mutation in this gene are associated with both Jervell and Lange-Nielsen and Romano-Ward forms of long-QT syndrome. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

KCNE1 Gene-Disease associations (from GenCC):

long QT syndrome 5
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
Jervell and Lange-Nielsen syndrome 2
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
Jervell and Lange-Nielsen syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
atrial fibrillation
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

KCNE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20441586).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000219.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KCNE1	NM_000219.6	MANE Select	c.123G>C	p.Lys41Asn	missense	Exon 4 of 4	NP_000210.2
KCNE1	NM_001127668.4		c.123G>C	p.Lys41Asn	missense	Exon 3 of 3	NP_001121140.1
KCNE1	NM_001127669.4		c.123G>C	p.Lys41Asn	missense	Exon 3 of 3	NP_001121141.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KCNE1	ENST00000399286.3	TSL:1 MANE Select	c.123G>C	p.Lys41Asn	missense	Exon 4 of 4	ENSP00000382226.2
KCNE1	ENST00000399289.7	TSL:1	c.123G>C	p.Lys41Asn	missense	Exon 3 of 3	ENSP00000382228.3
KCNE1	ENST00000416357.6	TSL:1	c.123G>C	p.Lys41Asn	missense	Exon 2 of 2	ENSP00000416258.2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

81652

Hom.:

Cov.:

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000795

AC:

AN:

251418

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000831

AC:

AN:

842560

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

418858

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16192

American (AMR)

AF:

0.00

AC:

AN:

28578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13658

East Asian (EAS)

AF:

0.00

AC:

AN:

18036

South Asian (SAS)

AF:

0.000143

AC:

AN:

48824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3408

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

644334

Other (OTH)

AF:

0.00

AC:

AN:

34160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

81652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

39866

African (AFR)

AF:

0.00

AC:

AN:

19090

American (AMR)

AF:

0.00

AC:

AN:

9028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1754

East Asian (EAS)

AF:

0.00

AC:

AN:

2252

South Asian (SAS)

AF:

0.00

AC:

AN:

2410

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6858

Middle Eastern (MID)

AF:

0.00

AC:

AN:

168

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

38590

Other (OTH)

AF:

0.00

AC:

AN:

1128

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cardiovascular phenotype (1)

Long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.25

CADD

Benign

6.4

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.40

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.55

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.20

MetaSVM

Uncertain

-0.25

MutationAssessor

Uncertain

2.0

PhyloP100

-0.63

PrimateAI

Benign

0.28

PROVEAN

Benign

1.2

REVEL

Benign

0.19

Sift

Benign

0.39

Sift4G

Benign

0.43

Polyphen

0.20

Vest4

0.038

MutPred

0.29

Loss of ubiquitination at K41 (P = 0.0056)

MVP

0.83

MPC

0.087

ClinPred

0.054

GERP RS

2.2

Varity_R

0.043

gMVP

0.49

Mutation Taster

=83/17

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over