NM_002249.6:c.224_241delAGCAGCAGCAGCAGCAGC

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_002249.6(KCNN3):c.224_241delAGCAGCAGCAGCAGCAGC(p.Gln75_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 0.0000611 in 1,506,512 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Benign (★).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000060 ( 1 hom. )

Consequence

KCNN3
NM_002249.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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: Likely_benign. The variant received -2 ACMG points.

BP6

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN3	NM_002249.6 link	c.224_241delAGCAGCAGCAGCAGCAGC	p.Gln75_Gln80del	disruptive_inframe_deletion	Exon 1 of 8	ENST00000271915.9	NP_002240.3	Q9UGI6-1
KCNN3	NM_001204087.2 link	c.224_241delAGCAGCAGCAGCAGCAGC	p.Gln75_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.224_241delAGCAGCAGCAGCAGCAGC	p.Gln75_Gln80del	disruptive_inframe_deletion	Exon 1 of 8	1	NM_002249.6	ENSP00000271915.3		Q9UGI6-1

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

African (AFR)

AF:

0.0000321

AC:

AN:

31108

American (AMR)

AF:

0.0000563

AC:

AN:

35514

Ashkenazi Jewish (ASJ)

AF:

0.0000401

AC:

AN:

24960

East Asian (EAS)

AF:

0.0000281

AC:

AN:

35568

South Asian (SAS)

AF:

0.000279

AC:

AN:

78742

European-Finnish (FIN)

AF:

0.0000433

AC:

AN:

46138

Middle Eastern (MID)

AF:

0.000902

AC:

AN:

4434

European-Non Finnish (NFE)

AF:

0.0000447

AC:

AN:

1051856

Other (OTH)

AF:

0.0000352

AC:

AN:

56804

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

Exome 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

GnomAD4 genome

AF:

0.0000707

AC:

AN:

141388

Hom.:

Cov.:

AF XY:

0.0000735

AC XY:

AN XY:

68016

show subpopulations

African (AFR)

AF:

0.000106

AC:

AN:

37840

American (AMR)

AF:

0.00

AC:

AN:

14158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3376

East Asian (EAS)

AF:

0.00

AC:

AN:

4612

South Asian (SAS)

AF:

0.000990

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:

0.0000307

AC:

AN:

65186

Other (OTH)

AF:

0.00

AC:

AN:

1902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

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

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.4

Mutation Taster

=165/35

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