Variant 1-154869723-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_002249.6(KCNN3):c.241_242insAGCAGCAGC(p.Gln78_Gln80dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.13 ( 1519 hom., cov: 0)

Exomes 𝑓: 0.12 ( 2021 hom. )

Failed GnomAD Quality Control

Consequence

KCNN3
NM_002249.6 inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

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]

KCNN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 1-154869723-G-GGCTGCTGCT is Benign according to our data. Variant chr1-154869723-G-GGCTGCTGCT is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 403006.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNN3	NM_002249.6 linkuse as main transcript	c.241_242insAGCAGCAGC	p.Gln78_Gln80dup	inframe_insertion	1/8	ENST00000271915.9
KCNN3	NM_001204087.2 linkuse as main transcript	c.241_242insAGCAGCAGC	p.Gln78_Gln80dup	inframe_insertion	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNN3	ENST00000271915.9 linkuse as main transcript	c.241_242insAGCAGCAGC	p.Gln78_Gln80dup	inframe_insertion	1/8	1	NM_002249.6	P1	Q9UGI6-1
KCNN3	ENST00000618040.4 linkuse as main transcript	c.241_242insAGCAGCAGC	p.Gln78_Gln80dup	inframe_insertion	1/9	5

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

18884

AN:

140982

Hom.:

1518

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.0747

Gnomad AMR

AF:

0.0819

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.0112

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.185

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.126

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.119

AC:

156714

AN:

1321026

Hom.:

2021

Cov.:

112

AF XY:

0.119

AC XY:

77685

AN XY:

653388

show subpopulations

Gnomad4 AFR exome

AF:

0.207

Gnomad4 AMR exome

AF:

0.0673

Gnomad4 ASJ exome

AF:

0.112

Gnomad4 EAS exome

AF:

0.0183

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.139

Gnomad4 NFE exome

AF:

0.119

Gnomad4 OTH exome

AF:

0.113

GnomAD4 genome

AF:

0.134

AC:

18902

AN:

141082

Hom.:

1519

Cov.:

AF XY:

0.135

AC XY:

9167

AN XY:

67870

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.0816

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.0113

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.113

Gnomad4 OTH

AF:

0.126

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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: Not present in ESP. LOF is NOT an established disease mechanism. Not enough evidence that the gene is associated with cardiomyopathy. Mice homozygous for a conditional gene switch displayed no overt phenotype. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over