NM_002249.6:c.236_241delAGCAGC

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP3BP6BS1BS2

The NM_002249.6(KCNN3):c.236_241delAGCAGC(p.Gln79_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 0.00316 in 1,504,596 control chromosomes in the GnomAD database, including 42 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.012 ( 36 hom., cov: 0)

Exomes 𝑓: 0.0022 ( 6 hom. )

Consequence

KCNN3
NM_002249.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

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

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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
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 -10 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_002249.6

BP6

Variant 1-154869723-GGCTGCT-G is Benign according to our data. Variant chr1-154869723-GGCTGCT-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1685389.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0125 (1767/141370) while in subpopulation AFR AF = 0.0411 (1553/37824). AF 95% confidence interval is 0.0394. There are 36 homozygotes in GnomAd4. There are 805 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 36 Unknown,AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002249.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNN3	NM_002249.6	MANE Select	c.236_241delAGCAGC	p.Gln79_Gln80del	disruptive_inframe_deletion	Exon 1 of 8	NP_002240.3
	KCNN3	NM_001204087.2		c.236_241delAGCAGC	p.Gln79_Gln80del	disruptive_inframe_deletion	Exon 1 of 9	NP_001191016.1	A0A087WYJ0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNN3	ENST00000271915.9	TSL:1 MANE Select	c.236_241delAGCAGC	p.Gln79_Gln80del	disruptive_inframe_deletion	Exon 1 of 8	ENSP00000271915.3	Q9UGI6-1
KCNN3	ENST00000618040.4	TSL:5	c.236_241delAGCAGC	p.Gln79_Gln80del	disruptive_inframe_deletion	Exon 1 of 9	ENSP00000481848.1	A0A087WYJ0
KCNN3	ENST00000874071.1		c.236_241delAGCAGC	p.Gln79_Gln80del	disruptive_inframe_deletion	Exon 1 of 7	ENSP00000544130.1

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1765

AN:

141268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00743

Gnomad ASJ

AF:

0.00474

Gnomad EAS

AF:

0.00130

Gnomad SAS

AF:

0.00321

Gnomad FIN

AF:

0.000548

Gnomad MID

AF:

0.0199

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.00903

GnomAD4 exome

AF:

0.00219

AC:

2982

AN:

1363226

Hom.:

AF XY:

0.00217

AC XY:

1465

AN XY:

673940

show subpopulations

African (AFR)

AF:

0.0427

AC:

1326

AN:

31032

American (AMR)

AF:

0.00403

AC:

143

AN:

35492

Ashkenazi Jewish (ASJ)

AF:

0.00473

AC:

118

AN:

24934

East Asian (EAS)

AF:

0.00101

AC:

AN:

35566

South Asian (SAS)

AF:

0.00419

AC:

329

AN:

78600

European-Finnish (FIN)

AF:

0.000347

AC:

AN:

46050

Middle Eastern (MID)

AF:

0.00678

AC:

AN:

4426

European-Non Finnish (NFE)

AF:

0.000728

AC:

765

AN:

1050424

Other (OTH)

AF:

0.00386

AC:

219

AN:

56702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

111

221

332

442

553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<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:

0.0125

AC:

1767

AN:

141370

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

805

AN XY:

68002

show subpopulations

African (AFR)

AF:

0.0411

AC:

1553

AN:

37824

American (AMR)

AF:

0.00742

AC:

105

AN:

14156

Ashkenazi Jewish (ASJ)

AF:

0.00474

AC:

AN:

3376

East Asian (EAS)

AF:

0.00130

AC:

AN:

4614

South Asian (SAS)

AF:

0.00322

AC:

AN:

4042

European-Finnish (FIN)

AF:

0.000548

AC:

AN:

9120

Middle Eastern (MID)

AF:

0.0213

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000706

AC:

AN:

65184

Other (OTH)

AF:

0.00894

AC:

AN:

1902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

149

224

298

373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Zimmermann-Laband syndrome 3 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Mutation Taster

=185/15

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over