rs200170681
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PP3_StrongBP6BS2
The NM_000890.5(KCNJ5):c.739G>A(p.Gly247Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000695 in 1,610,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G247G) has been classified as Likely benign.
Frequency
Consequence
NM_000890.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNJ5 | NM_000890.5 | c.739G>A | p.Gly247Arg | missense_variant | 2/3 | ENST00000529694.6 | |
KCNJ5 | NM_001354169.2 | c.739G>A | p.Gly247Arg | missense_variant | 3/4 | ||
KCNJ5 | XM_011542810.4 | c.739G>A | p.Gly247Arg | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNJ5 | ENST00000529694.6 | c.739G>A | p.Gly247Arg | missense_variant | 2/3 | 1 | NM_000890.5 | P1 | |
KCNJ5 | ENST00000338350.4 | c.739G>A | p.Gly247Arg | missense_variant | 3/4 | 1 | P1 | ||
KCNJ5 | ENST00000533599.1 | c.739G>A | p.Gly247Arg | missense_variant | 1/2 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000838 AC: 21AN: 250708Hom.: 0 AF XY: 0.0000738 AC XY: 10AN XY: 135478
GnomAD4 exome AF: 0.0000720 AC: 105AN: 1458628Hom.: 0 Cov.: 58 AF XY: 0.0000690 AC XY: 50AN XY: 724896
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74338
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, no assertion criteria provided | literature only | OMIM | Apr 01, 2014 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 23, 2020 | Published functional studies are inconsistent in their conclusions as to whether or not the G247R variant impacts channel function (Calloe et al., 2007; Murthy et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 17967416, 24420545, 30847666) - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 19, 2020 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at