21-34449576-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000219.6(KCNE1):c.59C>T(p.Thr20Ile) 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). Synonymous variant affecting the same amino acid position (i.e. T20T) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 12)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KCNE1
NM_000219.6 missense
NM_000219.6 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: -0.628
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]
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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=0.15690786).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNE1 | NM_000219.6 | c.59C>T | p.Thr20Ile | missense_variant | 4/4 | ENST00000399286.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNE1 | ENST00000399286.3 | c.59C>T | p.Thr20Ile | missense_variant | 4/4 | 1 | NM_000219.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 12
GnomAD3 genomes
Cov.:
12
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251242Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135852
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GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 933376Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0AN XY: 469214
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
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GnomAD4 genome Cov.: 12
GnomAD4 genome
Cov.:
12
ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
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:19322600). 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
D;D;D;D;D;D;D;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M;M;M;M;M
MutationTaster
Benign
N;N;N;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.;N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;.;.;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T
Polyphen
B;B;B;B;B;B;B;B
Vest4
MutPred
Loss of disorder (P = 0.0438);Loss of disorder (P = 0.0438);Loss of disorder (P = 0.0438);Loss of disorder (P = 0.0438);Loss of disorder (P = 0.0438);Loss of disorder (P = 0.0438);Loss of disorder (P = 0.0438);Loss of disorder (P = 0.0438);
MVP
MPC
0.080
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at