chr1-154869723-GGCTGCT-G
Variant summary
Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_002249.6(KCNN3):c.236_241delAGCAGC(p.Gln79_Gln80del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,504,596 control chromosomes in the GnomAD database, including 42 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.012 ( 36 hom., cov: 0)
Exomes 𝑓: 0.0022 ( 6 hom. )
Consequence
KCNN3
NM_002249.6 disruptive_inframe_deletion
NM_002249.6 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.12
Publications
18 publications found
Genes affected
KCNN3 (HGNC:6292): (potassium calcium-activated channel subfamily N member 3) Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. This gene belongs to the KCNN family of potassium channels. It encodes an integral membrane protein that forms a voltage-independent calcium-activated channel, which is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. This gene contains two CAG repeat regions in the coding sequence. It was thought that expansion of one or both of these repeats could lead to an increased susceptibility to schizophrenia or bipolar disorder, but studies indicate that this is probably not the case. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]
KCNN3 Gene-Disease associations (from GenCC):
- Zimmermann-Laband syndrome 3Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- Zimmermann-Laband syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- schizophreniaInheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -9 ACMG points.
BP6
Variant 1-154869723-GGCTGCT-G is Benign according to our data. Variant chr1-154869723-GGCTGCT-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1685389. Variant chr1-154869723-GGCTGCT-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1685389. Variant chr1-154869723-GGCTGCT-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1685389. Variant chr1-154869723-GGCTGCT-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1685389. Variant chr1-154869723-GGCTGCT-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1685389.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0125 (1767/141370) while in subpopulation AFR AF = 0.0411 (1553/37824). AF 95% confidence interval is 0.0394. There are 36 homozygotes in GnomAd4. There are 805 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 36 Unknown,AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNN3 | NM_002249.6 | c.236_241delAGCAGC | p.Gln79_Gln80del | disruptive_inframe_deletion | Exon 1 of 8 | ENST00000271915.9 | NP_002240.3 | |
KCNN3 | NM_001204087.2 | c.236_241delAGCAGC | p.Gln79_Gln80del | disruptive_inframe_deletion | Exon 1 of 9 | NP_001191016.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0125 AC: 1765AN: 141268Hom.: 36 Cov.: 0 show subpopulations
GnomAD3 genomes
AF:
AC:
1765
AN:
141268
Hom.:
Cov.:
0
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:
GnomAD4 exome AF: 0.00219 AC: 2982AN: 1363226Hom.: 6 AF XY: 0.00217 AC XY: 1465AN XY: 673940 show subpopulations
GnomAD4 exome
AF:
AC:
2982
AN:
1363226
Hom.:
AF XY:
AC XY:
1465
AN XY:
673940
show subpopulations
African (AFR)
AF:
AC:
1326
AN:
31032
American (AMR)
AF:
AC:
143
AN:
35492
Ashkenazi Jewish (ASJ)
AF:
AC:
118
AN:
24934
East Asian (EAS)
AF:
AC:
36
AN:
35566
South Asian (SAS)
AF:
AC:
329
AN:
78600
European-Finnish (FIN)
AF:
AC:
16
AN:
46050
Middle Eastern (MID)
AF:
AC:
30
AN:
4426
European-Non Finnish (NFE)
AF:
AC:
765
AN:
1050424
Other (OTH)
AF:
AC:
219
AN:
56702
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.474
Heterozygous variant carriers
0
111
221
332
442
553
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
62
124
186
248
310
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome AF: 0.0125 AC: 1767AN: 141370Hom.: 36 Cov.: 0 AF XY: 0.0118 AC XY: 805AN XY: 68002 show subpopulations
GnomAD4 genome
AF:
AC:
1767
AN:
141370
Hom.:
Cov.:
0
AF XY:
AC XY:
805
AN XY:
68002
show subpopulations
African (AFR)
AF:
AC:
1553
AN:
37824
American (AMR)
AF:
AC:
105
AN:
14156
Ashkenazi Jewish (ASJ)
AF:
AC:
16
AN:
3376
East Asian (EAS)
AF:
AC:
6
AN:
4614
South Asian (SAS)
AF:
AC:
13
AN:
4042
European-Finnish (FIN)
AF:
AC:
5
AN:
9120
Middle Eastern (MID)
AF:
AC:
6
AN:
282
European-Non Finnish (NFE)
AF:
AC:
46
AN:
65184
Other (OTH)
AF:
AC:
17
AN:
1902
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
75
149
224
298
373
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Zimmermann-Laband syndrome 3 Uncertain:1
Jul 23, 2020
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:research
- -
not specified Benign:1
May 04, 2022
Mendelics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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