rs199473393
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000219.6(KCNE1):c.202T>A(p.Ser68Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: not found (cov: 17)
Consequence
KCNE1
NM_000219.6 missense
NM_000219.6 missense
Scores
6
11
1
Clinical Significance
Conservation
PhyloP100: 6.00
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 Uncertain_significance. Variant got 4 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, 13 uncertain in NM_000219.6
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNE1 | NM_000219.6 | c.202T>A | p.Ser68Thr | missense_variant | 4/4 | ENST00000399286.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNE1 | ENST00000399286.3 | c.202T>A | p.Ser68Thr | missense_variant | 4/4 | 1 | NM_000219.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 17
GnomAD3 genomes
?
Cov.:
17
GnomAD4 exome Cov.: 26
GnomAD4 exome
Cov.:
26
GnomAD4 genome ? Cov.: 17
GnomAD4 genome
?
Cov.:
17
ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
not provided Other:1
not provided, no classification provided | literature only | Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;D;D;D;D;D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;M;M;M;M;M;M
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;D;D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;.;.;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D;D
Polyphen
P;P;P;P;P;P;P;P
Vest4
MutPred
Loss of disorder (P = 0.0549);Loss of disorder (P = 0.0549);Loss of disorder (P = 0.0549);Loss of disorder (P = 0.0549);Loss of disorder (P = 0.0549);Loss of disorder (P = 0.0549);Loss of disorder (P = 0.0549);Loss of disorder (P = 0.0549);
MVP
MPC
0.40
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at