rs72554071
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_004982.4(KCNJ8):c.1265C>T(p.Ser422Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,613,842 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S422S) has been classified as Likely benign.
Frequency
Consequence
NM_004982.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNJ8 | NM_004982.4 | c.1265C>T | p.Ser422Leu | missense_variant | 3/3 | ENST00000240662.3 | |
LOC105369689 | XR_007063241.1 | n.631+5648G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNJ8 | ENST00000240662.3 | c.1265C>T | p.Ser422Leu | missense_variant | 3/3 | 1 | NM_004982.4 | P1 | |
ENST00000542489.1 | n.107-623G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00119 AC: 181AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00183 AC: 461AN: 251364Hom.: 4 AF XY: 0.00179 AC XY: 243AN XY: 135850
GnomAD4 exome AF: 0.00106 AC: 1552AN: 1461564Hom.: 9 Cov.: 31 AF XY: 0.00112 AC XY: 814AN XY: 727106
GnomAD4 genome ? AF: 0.00120 AC: 183AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.00109 AC XY: 81AN XY: 74464
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 28, 2020 | This variant is associated with the following publications: (PMID: 23414114, 23632791, 22562657, 20558321, 22056721, 22840528, 24068186, 24667784, 19120683, 30847666) - |
Uncertain significance, no assertion criteria provided | literature only | OMIM | Jul 01, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2022 | KCNJ8: PP2, BP4, BS2 - |
KCNJ8-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 10, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Brugada syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego | Jun 19, 2017 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 05, 2017 | This alteration is classified as 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