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

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_002249.6(KCNN3):c.241_242insAGCAGCAGCAGCAGCAGCAGC(p.Gln74_Gln80dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.049 ( 262 hom., cov: 0)

Exomes 𝑓: 0.056 ( 2497 hom. )

Failed GnomAD Quality Control

Consequence

KCNN3
NM_002249.6 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter 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]

KCNN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 1-154869723-G-GGCTGCTGCTGCTGCTGCTGCT is Benign according to our data. Variant chr1-154869723-G-GGCTGCTGCTGCTGCTGCTGCT is described in ClinVar as [Benign]. Clinvar id is 1685432.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN3	NM_002249.6 linkuse as main transcript	c.241_242insAGCAGCAGCAGCAGCAGCAGC	p.Gln74_Gln80dup	inframe_insertion	1/8	ENST00000271915.9	NP_002240.3
KCNN3	NM_001204087.2 linkuse as main transcript	c.241_242insAGCAGCAGCAGCAGCAGCAGC	p.Gln74_Gln80dup	inframe_insertion	1/9		NP_001191016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN3	ENST00000271915.9 linkuse as main transcript	c.241_242insAGCAGCAGCAGCAGCAGCAGC	p.Gln74_Gln80dup	inframe_insertion	1/8	1	NM_002249.6	ENSP00000271915	P1	Q9UGI6-1
KCNN3	ENST00000618040.4 linkuse as main transcript	c.241_242insAGCAGCAGCAGCAGCAGCAGC	p.Gln74_Gln80dup	inframe_insertion	1/9	5		ENSP00000481848

Frequencies

GnomAD3 genomes

AF:

0.0491

AC:

6935

AN:

141176

Hom.:

261

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0407

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.0326

Gnomad ASJ

AF:

0.0264

Gnomad EAS

AF:

0.0493

Gnomad SAS

AF:

0.0383

Gnomad FIN

AF:

0.0314

Gnomad MID

AF:

0.0298

Gnomad NFE

AF:

0.0602

Gnomad OTH

AF:

0.0515

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0562

AC:

76400

AN:

1358946

Hom.:

2497

Cov.:

112

AF XY:

0.0554

AC XY:

37211

AN XY:

671666

show subpopulations

Gnomad4 AFR exome

AF:

0.0426

Gnomad4 AMR exome

AF:

0.0308

Gnomad4 ASJ exome

AF:

0.0305

Gnomad4 EAS exome

AF:

0.0369

Gnomad4 SAS exome

AF:

0.0399

Gnomad4 FIN exome

AF:

0.0324

Gnomad4 NFE exome

AF:

0.0614

Gnomad4 OTH exome

AF:

0.0508

GnomAD4 genome

AF:

0.0492

AC:

6951

AN:

141278

Hom.:

262

Cov.:

AF XY:

0.0473

AC XY:

3212

AN XY:

67962

show subpopulations

Gnomad4 AFR

AF:

0.0410

Gnomad4 AMR

AF:

0.0325

Gnomad4 ASJ

AF:

0.0264

Gnomad4 EAS

AF:

0.0493

Gnomad4 SAS

AF:

0.0381

Gnomad4 FIN

AF:

0.0314

Gnomad4 NFE

AF:

0.0601

Gnomad4 OTH

AF:

0.0521

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

KCNN3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 20, 2024

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: 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