Variant chr21-34449615-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3PP5

The ENST00000399286.3(KCNE1):c.20C>T(p.Thr7Ile) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T7A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 13)

Consequence

KCNE1
ENST00000399286.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1O:2

Conservation

PhyloP100: 6.28

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.834

PP5

Variant 21-34449615-G-A is Pathogenic according to our data. Variant chr21-34449615-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 13476.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr21-34449615-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNE1	NM_000219.6 linkuse as main transcript	c.20C>T	p.Thr7Ile	missense_variant	4/4	ENST00000399286.3	NP_000210.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNE1	ENST00000399286.3 linkuse as main transcript	c.20C>T	p.Thr7Ile	missense_variant	4/4	1	NM_000219.6	ENSP00000382226	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251186

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1Other:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Jervell and Lange-Nielsen syndrome 2

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 1997

- -

Long QT syndrome 5

Other:1

not provided, no classification provided

in vitro

Roden Lab, Vanderbilt University Medical Center

- -

Congenital long QT syndrome

Other:1

not provided, no classification provided

literature only

Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust

This variant has been reported in the following publications (PMID:9354783). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.87

D;D;D;D;D;D;D;D

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.75

.;.;T;.;.;.;.;.

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.83

D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.8

M;M;M;M;M;M;M;M

MutationTaster

Benign

0.94

A;A;A;A;A;A;A;A;A;A;A;A

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.6

D;.;.;D;D;D;D;D

REVEL

Uncertain

0.59

Sift

Uncertain

0.0030

D;.;.;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;D;D;D;D

Vest4

0.57

MutPred

0.32

Loss of disorder (P = 0.0702);Loss of disorder (P = 0.0702);Loss of disorder (P = 0.0702);Loss of disorder (P = 0.0702);Loss of disorder (P = 0.0702);Loss of disorder (P = 0.0702);Loss of disorder (P = 0.0702);Loss of disorder (P = 0.0702);

MVP

0.96

MPC

0.45

ClinPred

0.97

GERP RS

4.8

Varity_R

0.41

gMVP

0.89

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