Variant 21-34449256-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000219.6(KCNE1):c.379C>A(p.Pro127Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 16)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNE1
NM_000219.6 missense

Scores

Clinical Significance

not provided no classification provided O:2

Conservation

PhyloP100: 1.33

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2428573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNE1	NM_000219.6 linkuse as main transcript	c.379C>A	p.Pro127Thr	missense_variant	4/4	ENST00000399286.3	NP_000210.2	P15382C7S316Q6FHJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNE1	ENST00000399286.3 linkuse as main transcript	c.379C>A	p.Pro127Thr	missense_variant	4/4	1	NM_000219.6	ENSP00000382226.2		P15382

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

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

AF:

0.00

AC:

AN:

832068

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

430014

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: not provided

Submissions summary: Other:2

Revision: no classification provided

LINK: link

Submissions by phenotype

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 as associated with Long QT syndrome in the following publications (PMID:10973849;PMID:15051636). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

0.12

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Uncertain

0.64

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

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.47

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

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.24

T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.17

MutationAssessor

Uncertain

2.5

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

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.35

N;.;.;N;N;N;N;N

REVEL

Uncertain

0.59

Sift

Uncertain

0.010

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

Sift4G

Uncertain

0.022

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

Polyphen

0.024

B;B;B;B;B;B;B;B

Vest4

0.11

MutPred

0.37

Gain of phosphorylation at P127 (P = 0.0295);Gain of phosphorylation at P127 (P = 0.0295);Gain of phosphorylation at P127 (P = 0.0295);Gain of phosphorylation at P127 (P = 0.0295);Gain of phosphorylation at P127 (P = 0.0295);Gain of phosphorylation at P127 (P = 0.0295);Gain of phosphorylation at P127 (P = 0.0295);Gain of phosphorylation at P127 (P = 0.0295);

MVP

0.87

MPC

0.14

ClinPred

0.11

GERP RS

0.67

Varity_R

0.042

gMVP

0.30

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