rs59172778
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_153766.3(KCNJ1):āc.1013T>Cā(p.Met338Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0097 in 1,614,112 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0077 ( 8 hom., cov: 32)
Exomes š: 0.0099 ( 80 hom. )
Consequence
KCNJ1
NM_153766.3 missense
NM_153766.3 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 4.85
Genes affected
KCNJ1 (HGNC:6255): (potassium inwardly rectifying channel subfamily J member 1) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. It is activated by internal ATP and probably plays an important role in potassium homeostasis. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Mutations in this gene have been associated with antenatal Bartter syndrome, which is characterized by salt wasting, hypokalemic alkalosis, hypercalciuria, and low blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.016446412).
BP6
Variant 11-128839231-A-G is Benign according to our data. Variant chr11-128839231-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 9158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-128839231-A-G is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00766 (1167/152284) while in subpopulation NFE AF= 0.012 (817/68026). AF 95% confidence interval is 0.0113. There are 8 homozygotes in gnomad4. There are 564 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNJ1 | NM_153766.3 | c.1013T>C | p.Met338Thr | missense_variant | 3/3 | ENST00000392666.6 | NP_722450.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNJ1 | ENST00000392666.6 | c.1013T>C | p.Met338Thr | missense_variant | 3/3 | 1 | NM_153766.3 | ENSP00000376434.1 |
Frequencies
GnomAD3 genomes AF: 0.00766 AC: 1166AN: 152166Hom.: 8 Cov.: 32
GnomAD3 genomes
AF:
AC:
1166
AN:
152166
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00728 AC: 1830AN: 251362Hom.: 17 AF XY: 0.00738 AC XY: 1002AN XY: 135854
GnomAD3 exomes
AF:
AC:
1830
AN:
251362
Hom.:
AF XY:
AC XY:
1002
AN XY:
135854
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00991 AC: 14492AN: 1461828Hom.: 80 Cov.: 33 AF XY: 0.00961 AC XY: 6988AN XY: 727222
GnomAD4 exome
AF:
AC:
14492
AN:
1461828
Hom.:
Cov.:
33
AF XY:
AC XY:
6988
AN XY:
727222
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00766 AC: 1167AN: 152284Hom.: 8 Cov.: 32 AF XY: 0.00757 AC XY: 564AN XY: 74468
GnomAD4 genome
AF:
AC:
1167
AN:
152284
Hom.:
Cov.:
32
AF XY:
AC XY:
564
AN XY:
74468
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
29
ALSPAC
AF:
AC:
38
ESP6500AA
AF:
AC:
8
ESP6500EA
AF:
AC:
81
ExAC
AF:
AC:
974
Asia WGS
AF:
AC:
6
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Pathogenic:1Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:5
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Nov 24, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 05, 2021 | This variant is associated with the following publications: (PMID: 9580661, 20981092, 8841184, 27884173, 12589089, 28492530, 29191167) - |
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Jun 08, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 18, 2022 | - - |
Bartter disease type 2 Pathogenic:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Molecular Genetics, Royal Melbourne Hospital | May 04, 2023 | European Non-Finnish population allele frequency is 1.112% (rs59172778, 1491/129090 alleles, 14 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, this variant is classified as BENIGN. Following criteria are met: BA1 - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 1996 | - - |
KCNJ1-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 26, 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). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
.;.;.;.;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;.;.;T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
.;.;.;.;N
MutationTaster
Benign
A;A;A;A;A
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
0.0040
.;.;.;.;B
Vest4
MVP
MPC
0.039
ClinPred
T
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