Variant chr1-154869723-GGCTGCTGCTGCTGCTGCT-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_002249.6(KCNN3):c.224_241del(p.Gln75_Gln80del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000611 in 1,506,512 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000060 ( 1 hom. )

Consequence

KCNN3
NM_002249.6 inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.39

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant 1-154869723-GGCTGCTGCTGCTGCTGCT-G is Benign according to our data. Variant chr1-154869723-GGCTGCTGCTGCTGCTGCT-G is described in ClinVar as [Benign]. Clinvar id is 1685442.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN3	NM_002249.6 linkuse as main transcript	c.224_241del	p.Gln75_Gln80del	inframe_deletion	1/8	ENST00000271915.9	NP_002240.3
KCNN3	NM_001204087.2 linkuse as main transcript	c.224_241del	p.Gln75_Gln80del	inframe_deletion	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.224_241del	p.Gln75_Gln80del	inframe_deletion	1/8	1	NM_002249.6	ENSP00000271915	P1	Q9UGI6-1
KCNN3	ENST00000618040.4 linkuse as main transcript	c.224_241del	p.Gln75_Gln80del	inframe_deletion	1/9	5		ENSP00000481848

Frequencies

GnomAD3 genomes

AF:

0.0000708

AC:

AN:

141286

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000988

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000307

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000601

AC:

AN:

1365124

Hom.:

AF XY:

0.0000682

AC XY:

AN XY:

674886

show subpopulations

Gnomad4 AFR exome

AF:

0.0000321

Gnomad4 AMR exome

AF:

0.0000563

Gnomad4 ASJ exome

AF:

0.0000401

Gnomad4 EAS exome

AF:

0.0000281

Gnomad4 SAS exome

AF:

0.000279

Gnomad4 FIN exome

AF:

0.0000433

Gnomad4 NFE exome

AF:

0.0000447

Gnomad4 OTH exome

AF:

0.0000352

GnomAD4 genome

AF:

0.0000707

AC:

AN:

141388

Hom.:

Cov.:

AF XY:

0.0000735

AC XY:

AN XY:

68016

show subpopulations

Gnomad4 AFR

AF:

0.000106

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000990

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000307

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

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

- -

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