rs199473358
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM1
The NM_000219.6(KCNE1):āc.235A>Gā(p.Asn79Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N79S) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 17)
Exomes š: 6.9e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KCNE1
NM_000219.6 missense
NM_000219.6 missense
Scores
3
10
5
Clinical Significance
Conservation
PhyloP100: 3.33
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 2 ACMG points.
PM1
?
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 11 uncertain in NM_000219.6
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNE1 | NM_000219.6 | c.235A>G | p.Asn79Asp | missense_variant | 4/4 | ENST00000399286.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNE1 | ENST00000399286.3 | c.235A>G | p.Asn79Asp | missense_variant | 4/4 | 1 | NM_000219.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 17
GnomAD3 genomes
?
Cov.:
17
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251436Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135914
GnomAD3 exomes
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.85e-7 AC: 1AN: 1459138Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 726026
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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1
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1459138
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29
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AN XY:
726026
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GnomAD4 genome ? Cov.: 17
GnomAD4 genome
?
Cov.:
17
ExAC
?
AF:
AC:
1
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 | - | This variant has been reported in the following publications (PMID:10428953). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;D;D;D;D;D;D
Eigen
Uncertain
Eigen_PC
Benign
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
N;.;.;N;N;N;N;N
REVEL
Pathogenic
Sift
Benign
D;.;.;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T;T;T
Polyphen
D;D;D;D;D;D;D;D
Vest4
MutPred
Gain of disorder (P = 0.1326);Gain of disorder (P = 0.1326);Gain of disorder (P = 0.1326);Gain of disorder (P = 0.1326);Gain of disorder (P = 0.1326);Gain of disorder (P = 0.1326);Gain of disorder (P = 0.1326);Gain of disorder (P = 0.1326);
MVP
MPC
0.22
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