1-154869723-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT-GGCTGCTGCTGCTGCTGCTGCT

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_002249.6(KCNN3):c.233_241delAGCAGCAGC(p.Gln78_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 0.00146 in 1,506,444 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0013 ( 2 hom. )

Consequence

KCNN3
NM_002249.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.12

Publications

18 publications found

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 Gene-Disease associations (from GenCC):

Zimmermann-Laband syndrome 3
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
Zimmermann-Laband syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
schizophrenia
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

KCNN3 links:

ENSG00000308854 (HGNC:):

ENSG00000308854 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP6

Variant 1-154869723-GGCTGCTGCT-G is Benign according to our data. Variant chr1-154869723-GGCTGCTGCT-G is described in CliVar as Benign/Likely_benign. Clinvar id is 1685424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154869723-GGCTGCTGCT-G is described in CliVar as Benign/Likely_benign. Clinvar id is 1685424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154869723-GGCTGCTGCT-G is described in CliVar as Benign/Likely_benign. Clinvar id is 1685424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154869723-GGCTGCTGCT-G is described in CliVar as Benign/Likely_benign. Clinvar id is 1685424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154869723-GGCTGCTGCT-G is described in CliVar as Benign/Likely_benign. Clinvar id is 1685424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 Unknown,AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN3	NM_002249.6 link	c.233_241delAGCAGCAGC	p.Gln78_Gln80del	disruptive_inframe_deletion	Exon 1 of 8	ENST00000271915.9	NP_002240.3	Q9UGI6-1
KCNN3	NM_001204087.2 link	c.233_241delAGCAGCAGC	p.Gln78_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
KCNN3	ENST00000271915.9 link	c.233_241delAGCAGCAGC	p.Gln78_Gln80del	disruptive_inframe_deletion	Exon 1 of 8	1	NM_002249.6	ENSP00000271915.3		Q9UGI6-1

Frequencies

GnomAD3 genomes

AF:

0.00254

AC:

359

AN:

141284

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00400

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.000707

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00475

Gnomad SAS

AF:

0.00247

Gnomad FIN

AF:

0.00855

Gnomad MID

AF:

0.00331

Gnomad NFE

AF:

0.000936

Gnomad OTH

AF:

0.00266

GnomAD4 exome

AF:

0.00135

AC:

1839

AN:

1365058

Hom.:

AF XY:

0.00134

AC XY:

903

AN XY:

674866

show subpopulations

African (AFR)

AF:

0.00415

AC:

129

AN:

31060

American (AMR)

AF:

0.00130

AC:

AN:

35514

Ashkenazi Jewish (ASJ)

AF:

0.000160

AC:

AN:

24960

East Asian (EAS)

AF:

0.00225

AC:

AN:

35568

South Asian (SAS)

AF:

0.00160

AC:

126

AN:

78742

European-Finnish (FIN)

AF:

0.00694

AC:

320

AN:

46130

Middle Eastern (MID)

AF:

0.000902

AC:

AN:

4434

European-Non Finnish (NFE)

AF:

0.000989

AC:

1040

AN:

1051846

Other (OTH)

AF:

0.00158

AC:

AN:

56804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

138

206

275

344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00254

AC:

359

AN:

141386

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

209

AN XY:

68012

show subpopulations

African (AFR)

AF:

0.00399

AC:

151

AN:

37840

American (AMR)

AF:

0.000706

AC:

AN:

14158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3376

East Asian (EAS)

AF:

0.00477

AC:

AN:

4614

South Asian (SAS)

AF:

0.00248

AC:

AN:

4040

European-Finnish (FIN)

AF:

0.00855

AC:

AN:

9118

Middle Eastern (MID)

AF:

0.00355

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000936

AC:

AN:

65186

Other (OTH)

AF:

0.00263

AC:

AN:

1902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

292

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2022

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KCNN3: PM4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Mutation Taster

=183/17

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over