rs1131820

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002249.6(KCNN3):c.1047T>C(p.Asn349Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 1,613,634 control chromosomes in the GnomAD database, including 442,919 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 39672 hom., cov: 34)

Exomes 𝑓: 0.74 ( 403247 hom. )

Consequence

KCNN3
NM_002249.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.41

Publications

32 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 1-154772376-A-G is Benign according to our data. Variant chr1-154772376-A-G is described in ClinVar as [Benign]. Clinvar id is 403002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN3	NM_002249.6 link	c.1047T>C	p.Asn349Asn	synonymous_variant	Exon 3 of 8	ENST00000271915.9	NP_002240.3	Q9UGI6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNN3	ENST00000271915.9 link	c.1047T>C	p.Asn349Asn	synonymous_variant	Exon 3 of 8	1	NM_002249.6	ENSP00000271915.3	Q9UGI6-1
KCNN3	ENST00000361147.8 link	c.132T>C	p.Asn44Asn	synonymous_variant	Exon 3 of 8	1		ENSP00000354764.4	Q9UGI6-2
KCNN3	ENST00000358505.2 link	c.108T>C	p.Asn36Asn	synonymous_variant	Exon 3 of 8	1		ENSP00000351295.2	Q9UGI6-3
KCNN3	ENST00000618040.4 link	c.1047T>C	p.Asn349Asn	synonymous_variant	Exon 3 of 9	5		ENSP00000481848.1	A0A087WYJ0

Frequencies

GnomAD3 genomes

AF:

0.717

AC:

109036

AN:

152082

Hom.:

39653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.618

Gnomad AMI

AF:

0.558

Gnomad AMR

AF:

0.819

Gnomad ASJ

AF:

0.763

Gnomad EAS

AF:

0.982

Gnomad SAS

AF:

0.839

Gnomad FIN

AF:

0.692

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.728

Gnomad OTH

AF:

0.738

GnomAD2 exomes

AF:

0.769

AC:

192467

AN:

250314

AF XY:

0.768

show subpopulations

Gnomad AFR exome

AF:

0.615

Gnomad AMR exome

AF:

0.877

Gnomad ASJ exome

AF:

0.756

Gnomad EAS exome

AF:

0.986

Gnomad FIN exome

AF:

0.693

Gnomad NFE exome

AF:

0.722

Gnomad OTH exome

AF:

0.754

GnomAD4 exome

AF:

0.740

AC:

1081752

AN:

1461434

Hom.:

403247

Cov.:

AF XY:

0.743

AC XY:

539901

AN XY:

727010

show subpopulations

African (AFR)

AF:

0.616

AC:

20627

AN:

33474

American (AMR)

AF:

0.869

AC:

38819

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.751

AC:

19629

AN:

26130

East Asian (EAS)

AF:

0.984

AC:

39050

AN:

39696

South Asian (SAS)

AF:

0.834

AC:

71912

AN:

86238

European-Finnish (FIN)

AF:

0.689

AC:

36782

AN:

53348

Middle Eastern (MID)

AF:

0.803

AC:

4628

AN:

5766

European-Non Finnish (NFE)

AF:

0.724

AC:

805142

AN:

1111708

Other (OTH)

AF:

0.748

AC:

45163

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

16195

32390

48584

64779

80974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.717

AC:

109110

AN:

152200

Hom.:

39672

Cov.:

AF XY:

0.722

AC XY:

53715

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.618

AC:

25657

AN:

41526

American (AMR)

AF:

0.819

AC:

12538

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.763

AC:

2647

AN:

3470

East Asian (EAS)

AF:

0.982

AC:

5076

AN:

5168

South Asian (SAS)

AF:

0.839

AC:

4044

AN:

4822

European-Finnish (FIN)

AF:

0.692

AC:

7330

AN:

10594

Middle Eastern (MID)

AF:

0.816

AC:

240

AN:

294

European-Non Finnish (NFE)

AF:

0.728

AC:

49509

AN:

67990

Other (OTH)

AF:

0.738

AC:

1561

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1654

3308

4963

6617

8271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.731

Hom.:

85385

Bravo

AF:

0.723

Asia WGS

AF:

0.874

AC:

3035

AN:

3478

EpiCase

AF:

0.737

EpiControl

AF:

0.738

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Zimmermann-Laband syndrome 3

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.2

(source)

DANN

Benign

0.50

PhyloP100

-1.4

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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rs1131820

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