Variant rs1218586 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002249.6(KCNN3):c.933+9186T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.967 in 1,600,466 control chromosomes in the GnomAD database, including 748,599 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.96 ( 69930 hom., cov: 34)

Exomes 𝑓: 0.97 ( 678669 hom. )

Consequence

KCNN3
NM_002249.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.191

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.933+9186T>G		intron_variant		ENST00000271915.9	NP_002240.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
KCNN3	ENST00000271915.9 linkuse as main transcript	c.933+9186T>G	intron_variant	1	NM_002249.6	ENSP00000271915	P1	Q9UGI6-1
KCNN3	ENST00000358505.2 linkuse as main transcript	c.-7+8103T>G	intron_variant	1		ENSP00000351295		Q9UGI6-3
KCNN3	ENST00000618040.4 linkuse as main transcript	c.933+9186T>G	intron_variant	5		ENSP00000481848
KCNN3	ENST00000361147.8 linkuse as main transcript		upstream_gene_variant	1		ENSP00000354764		Q9UGI6-2

Frequencies

GnomAD3 genomes

AF:

0.958

AC:

145801

AN:

152210

Hom.:

69876

Cov.:

show subpopulations

Gnomad AFR

AF:

0.929

Gnomad AMI

AF:

0.959

Gnomad AMR

AF:

0.961

Gnomad ASJ

AF:

0.945

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.947

Gnomad FIN

AF:

0.986

Gnomad MID

AF:

0.908

Gnomad NFE

AF:

0.969

Gnomad OTH

AF:

0.952

GnomAD4 exome

AF:

0.968

AC:

1401869

AN:

1448138

Hom.:

678669

Cov.:

AF XY:

0.967

AC XY:

695903

AN XY:

719650

show subpopulations

Gnomad4 AFR exome

AF:

0.921

Gnomad4 AMR exome

AF:

0.975

Gnomad4 ASJ exome

AF:

0.949

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.948

Gnomad4 FIN exome

AF:

0.985

Gnomad4 NFE exome

AF:

0.970

Gnomad4 OTH exome

AF:

0.962

GnomAD4 genome

AF:

0.958

AC:

145914

AN:

152328

Hom.:

69930

Cov.:

AF XY:

0.959

AC XY:

71450

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.929

Gnomad4 AMR

AF:

0.961

Gnomad4 ASJ

AF:

0.945

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.948

Gnomad4 FIN

AF:

0.986

Gnomad4 NFE

AF:

0.969

Gnomad4 OTH

AF:

0.952

Alfa

AF:

0.964

Hom.:

25180

Bravo

AF:

0.954

Asia WGS

AF:

0.976

AC:

3395

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over