1-154869723-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT-GGCTGCTGCTGCTGCTGCT

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_002249.6(KCNN3):c.230_241delAGCAGCAGCAGC(p.Gln77_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 0.000694 in 1,506,500 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00069 ( 0 hom. )

Consequence

KCNN3
NM_002249.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.39

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 -8 ACMG points.

BP6

Variant 1-154869723-GGCTGCTGCTGCT-G is Benign according to our data. Variant chr1-154869723-GGCTGCTGCTGCT-G is described in CliVar as Benign/Likely_benign. Clinvar id is 1685397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154869723-GGCTGCTGCTGCT-G is described in CliVar as Benign/Likely_benign. Clinvar id is 1685397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154869723-GGCTGCTGCTGCT-G is described in CliVar as Benign/Likely_benign. Clinvar id is 1685397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154869723-GGCTGCTGCTGCT-G is described in CliVar as Benign/Likely_benign. Clinvar id is 1685397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154869723-GGCTGCTGCTGCT-G is described in CliVar as Benign/Likely_benign. Clinvar id is 1685397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN3	NM_002249.6 link	c.230_241delAGCAGCAGCAGC	p.Gln77_Gln80del	disruptive_inframe_deletion	Exon 1 of 8	ENST00000271915.9	NP_002240.3	Q9UGI6-1
KCNN3	NM_001204087.2 link	c.230_241delAGCAGCAGCAGC	p.Gln77_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.230_241delAGCAGCAGCAGC	p.Gln77_Gln80del	disruptive_inframe_deletion	Exon 1 of 8	1	NM_002249.6	ENSP00000271915.3		Q9UGI6-1

Frequencies

GnomAD3 genomes

AF:

0.000743

AC:

105

AN:

141284

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000371

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00226

Gnomad ASJ

AF:

0.000592

Gnomad EAS

AF:

0.00454

Gnomad SAS

AF:

0.000988

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000383

Gnomad OTH

AF:

0.00372

GnomAD4 exome

AF:

0.000689

AC:

941

AN:

1365114

Hom.:

AF XY:

0.000650

AC XY:

439

AN XY:

674884

show subpopulations

African (AFR)

AF:

0.000225

AC:

AN:

31108

American (AMR)

AF:

0.00527

AC:

187

AN:

35504

Ashkenazi Jewish (ASJ)

AF:

0.000321

AC:

AN:

24958

East Asian (EAS)

AF:

0.00503

AC:

179

AN:

35568

South Asian (SAS)

AF:

0.000622

AC:

AN:

78748

European-Finnish (FIN)

AF:

0.0000867

AC:

AN:

46138

Middle Eastern (MID)

AF:

0.000226

AC:

AN:

4434

European-Non Finnish (NFE)

AF:

0.000442

AC:

465

AN:

1051852

Other (OTH)

AF:

0.000722

AC:

AN:

56804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<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:

0.000736

AC:

104

AN:

141386

Hom.:

Cov.:

AF XY:

0.000750

AC XY:

AN XY:

68014

show subpopulations

African (AFR)

AF:

0.000370

AC:

AN:

37840

American (AMR)

AF:

0.00226

AC:

AN:

14156

Ashkenazi Jewish (ASJ)

AF:

0.000592

AC:

AN:

3376

East Asian (EAS)

AF:

0.00455

AC:

AN:

4614

South Asian (SAS)

AF:

0.000742

AC:

AN:

4042

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9120

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000384

AC:

AN:

65184

Other (OTH)

AF:

0.00368

AC:

AN:

1902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

May 04, 2022

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Oct 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KCNN3: PM4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.4

Mutation Taster

=174/26

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over