GeneBe

rs193922907

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_002249.6(KCNN3):​c.239_241delAGC​(p.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 0.0431 in 1,505,328 control chromosomes in the GnomAD database, including 408 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 151 hom., cov: 0)
Exomes 𝑓: 0.043 ( 257 hom. )

Consequence

KCNN3
NM_002249.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.12
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 1-154869723-GGCT-G is Benign according to our data. Variant chr1-154869723-GGCT-G is described in ClinVar as [Benign]. Clinvar id is 403004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0575 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNN3NM_002249.6 linkc.239_241delAGC p.Gln80del disruptive_inframe_deletion Exon 1 of 8 ENST00000271915.9 NP_002240.3 Q9UGI6-1
KCNN3NM_001204087.2 linkc.239_241delAGC p.Gln80del disruptive_inframe_deletion Exon 1 of 9 NP_001191016.1 Q9UGI6A0A087WYJ0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNN3ENST00000271915.9 linkc.239_241delAGC p.Gln80del disruptive_inframe_deletion Exon 1 of 8 1 NM_002249.6 ENSP00000271915.3 Q9UGI6-1
KCNN3ENST00000618040.4 linkc.239_241delAGC p.Gln80del disruptive_inframe_deletion Exon 1 of 9 5 ENSP00000481848.1 A0A087WYJ0

Frequencies

GnomAD3 genomes
AF:
0.0454
AC:
6409
AN:
141212
Hom.:
151
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0595
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0296
Gnomad ASJ
AF:
0.0353
Gnomad EAS
AF:
0.00173
Gnomad SAS
AF:
0.0383
Gnomad FIN
AF:
0.0477
Gnomad MID
AF:
0.0364
Gnomad NFE
AF:
0.0448
Gnomad OTH
AF:
0.0521
GnomAD4 exome
AF:
0.0429
AC:
58521
AN:
1364014
Hom.:
257
AF XY:
0.0425
AC XY:
28625
AN XY:
674284
show subpopulations
Gnomad4 AFR exome
AF:
0.0587
Gnomad4 AMR exome
AF:
0.0233
Gnomad4 ASJ exome
AF:
0.0320
Gnomad4 EAS exome
AF:
0.00231
Gnomad4 SAS exome
AF:
0.0378
Gnomad4 FIN exome
AF:
0.0464
Gnomad4 NFE exome
AF:
0.0449
Gnomad4 OTH exome
AF:
0.0440
GnomAD4 genome
AF:
0.0454
AC:
6415
AN:
141314
Hom.:
151
Cov.:
0
AF XY:
0.0450
AC XY:
3058
AN XY:
67988
show subpopulations
Gnomad4 AFR
AF:
0.0595
Gnomad4 AMR
AF:
0.0295
Gnomad4 ASJ
AF:
0.0353
Gnomad4 EAS
AF:
0.00173
Gnomad4 SAS
AF:
0.0384
Gnomad4 FIN
AF:
0.0477
Gnomad4 NFE
AF:
0.0448
Gnomad4 OTH
AF:
0.0515

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
May 04, 2022
Mendelics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Mar 28, 2016
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency (18 homozygotes in ExAC) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3831942; hg19: chr1-154842199; API