NM_000219.6:c.238G>C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM1BP4_Moderate

The NM_000219.6(KCNE1):c.238G>C(p.Val80Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,459,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V80G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000070 ( 0 hom., cov: 18)

Exomes 𝑓: 0.000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNE1
NM_000219.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.34

Publications

7 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: Uncertain_significance. The variant received 0 ACMG points.

PM1

In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 110 uncertain in NM_000219.6

BP4

Computational evidence support a benign effect (MetaRNN=0.24568343).

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.238G>C	p.Val80Leu	missense	Exon 4 of 4	NP_000210.2
KCNE1	NM_001127668.4		c.238G>C	p.Val80Leu	missense	Exon 3 of 3	NP_001121140.1
KCNE1	NM_001127669.4		c.238G>C	p.Val80Leu	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.238G>C	p.Val80Leu	missense	Exon 4 of 4	ENSP00000382226.2
KCNE1	ENST00000399289.7	TSL:1	c.238G>C	p.Val80Leu	missense	Exon 3 of 3	ENSP00000382228.3
KCNE1	ENST00000416357.6	TSL:1	c.238G>C	p.Val80Leu	missense	Exon 2 of 2	ENSP00000416258.2

Frequencies

GnomAD3 genomes

AF:

0.00000696

AC:

AN:

143684

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.000231

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

251434

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1459530

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

726200

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.000101

AC:

AN:

39690

South Asian (SAS)

AF:

0.000116

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000451

AC:

AN:

1109804

Other (OTH)

AF:

0.0000166

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.573

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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: AS_VQSR

AF:

0.00000696

AC:

AN:

143684

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

69632

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39150

American (AMR)

AF:

0.00

AC:

AN:

14214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3318

East Asian (EAS)

AF:

0.00

AC:

AN:

4710

South Asian (SAS)

AF:

0.000231

AC:

AN:

4322

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65016

Other (OTH)

AF:

0.00

AC:

AN:

1924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Uncertain

0.070

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Uncertain

0.45

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.25

MetaSVM

Uncertain

-0.079

MutationAssessor

Uncertain

2.7

PhyloP100

1.3

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.29

REVEL

Uncertain

0.56

Sift

Benign

0.42

Sift4G

Benign

0.18

Polyphen

0.095

Vest4

0.25

MutPred

0.35

Gain of catalytic residue at V80 (P = 0.0721)

MVP

0.84

MPC

0.076

ClinPred

0.074

GERP RS

3.3

Varity_R

0.071

gMVP

0.59

Mutation Taster

=86/14

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over