rs28933384
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3PP5
The NM_000219.6(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).
Frequency
Genomes: not found (cov: 13)
Consequence
KCNE1
NM_000219.6 missense
NM_000219.6 missense
Scores
7
9
2
Clinical Significance
Conservation
PhyloP100: 6.28
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.
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 | UniProt |
---|---|---|---|---|---|---|---|
KCNE1 | NM_000219.6 | c.20C>T | p.Thr7Ile | missense_variant | 4/4 | ENST00000399286.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNE1 | ENST00000399286.3 | c.20C>T | p.Thr7Ile | missense_variant | 4/4 | 1 | NM_000219.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 13
GnomAD3 genomes
?
Cov.:
13
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251186Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135850
GnomAD3 exomes
AF:
AC:
1
AN:
251186
Hom.:
AF XY:
AC XY:
0
AN XY:
135850
Gnomad AFR exome
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GnomAD4 exome Cov.: 11
GnomAD4 exome
Cov.:
11
GnomAD4 genome ? Cov.: 13
GnomAD4 genome
?
Cov.:
13
ExAC
?
AF:
AC:
1
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
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 | - - |
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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;D;D;D;D;D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;M;M;M;M;M;M
MutationTaster
Benign
A;A;A;A;A;A;A;A;A;A;A;A
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.;.;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;.;.;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D
Polyphen
D;D;D;D;D;D;D;D
Vest4
MutPred
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
MPC
0.45
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