NM_002249.6:c.239_241dupAGC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_002249.6(KCNN3):c.239_241dupAGC(p.Gln80dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 52 hom., cov: 0)

Exomes 𝑓: 0.011 ( 16 hom. )

Failed GnomAD Quality Control

Consequence

KCNN3
NM_002249.6 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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 -16 ACMG points.

BP6

Variant 1-154869723-G-GGCT is Benign according to our data. Variant chr1-154869723-G-GGCT is described in CliVar as Benign. Clinvar id is 1685458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154869723-G-GGCT is described in CliVar as Benign. Clinvar id is 1685458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154869723-G-GGCT is described in CliVar as Benign. Clinvar id is 1685458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154869723-G-GGCT is described in CliVar as Benign. Clinvar id is 1685458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154869723-G-GGCT is described in CliVar as Benign. Clinvar id is 1685458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0211 (2978/141352) while in subpopulation AFR AF = 0.0451 (1705/37826). AF 95% confidence interval is 0.0433. There are 52 homozygotes in GnomAd4. There are 1409 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 52 Unknown,AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN3	NM_002249.6 link	c.239_241dupAGC	p.Gln80dup	conservative_inframe_insertion	Exon 1 of 8	ENST00000271915.9	NP_002240.3	Q9UGI6-1
KCNN3	NM_001204087.2 link	c.239_241dupAGC	p.Gln80dup	conservative_inframe_insertion	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.239_241dupAGC	p.Gln80dup	conservative_inframe_insertion	Exon 1 of 8	1	NM_002249.6	ENSP00000271915.3		Q9UGI6-1

Frequencies

GnomAD3 genomes

AF:

0.0210

AC:

2973

AN:

141252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0451

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.0145

Gnomad EAS

AF:

0.00691

Gnomad SAS

AF:

0.0240

Gnomad FIN

AF:

0.0113

Gnomad MID

AF:

0.0232

Gnomad NFE

AF:

0.00980

Gnomad OTH

AF:

0.0133

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0105

AC:

14325

AN:

1363626

Hom.:

Cov.:

112

AF XY:

0.0108

AC XY:

7251

AN XY:

674126

show subpopulations

African (AFR)

AF:

0.0445

AC:

1381

AN:

31042

American (AMR)

AF:

0.0105

AC:

371

AN:

35494

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

366

AN:

24934

East Asian (EAS)

AF:

0.00568

AC:

202

AN:

35560

South Asian (SAS)

AF:

0.0222

AC:

1746

AN:

78676

European-Finnish (FIN)

AF:

0.0105

AC:

482

AN:

46094

Middle Eastern (MID)

AF:

0.0153

AC:

AN:

4432

European-Non Finnish (NFE)

AF:

0.00848

AC:

8908

AN:

1050670

Other (OTH)

AF:

0.0141

AC:

801

AN:

56724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

746

1492

2238

2984

3730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.0211

AC:

2978

AN:

141352

Hom.:

Cov.:

AF XY:

0.0207

AC XY:

1409

AN XY:

68000

show subpopulations

African (AFR)

AF:

0.0451

AC:

1705

AN:

37826

American (AMR)

AF:

0.0225

AC:

319

AN:

14150

Ashkenazi Jewish (ASJ)

AF:

0.0145

AC:

AN:

3376

East Asian (EAS)

AF:

0.00694

AC:

AN:

4614

South Asian (SAS)

AF:

0.0245

AC:

AN:

4042

European-Finnish (FIN)

AF:

0.0113

AC:

103

AN:

9120

Middle Eastern (MID)

AF:

0.0248

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.00979

AC:

638

AN:

65170

Other (OTH)

AF:

0.0137

AC:

AN:

1902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

130

260

391

521

651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:2

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Mutation Taster

=75/25

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