NM_000219.6:c.139G>A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 4P and 9B. PM1PM5BP4_StrongBP6BS2
The NM_000219.6(KCNE1):c.139G>A(p.Val47Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000794 in 1,083,708 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V47F) has been classified as Pathogenic.
Frequency
Consequence
NM_000219.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000478 AC: 4AN: 83714Hom.: 1 Cov.: 14
GnomAD3 exomes AF: 0.000278 AC: 70AN: 251432Hom.: 1 AF XY: 0.000258 AC XY: 35AN XY: 135910
GnomAD4 exome AF: 0.0000820 AC: 82AN: 999994Hom.: 4 Cov.: 21 AF XY: 0.000111 AC XY: 56AN XY: 504598
GnomAD4 genome AF: 0.0000478 AC: 4AN: 83714Hom.: 1 Cov.: 14 AF XY: 0.0000978 AC XY: 4AN XY: 40886
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23631430, 21907427, 30245029, 24710009, 28807990, 29309402, 33919104) -
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not specified Benign:1
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Cardiomyopathy Benign:1
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Long QT syndrome Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Long QT syndrome 5 Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at