rs11584635

Variant names:

• chr1-154788489-T-C
• rs11584635
• NM_002249.6:c.1030-16096A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002249.6(KCNN3):​c.1030-16096A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,124 control chromosomes in the GnomAD database, including 5,692 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5692 hom., cov: 32)
• Consequence: KCNN3 NM_002249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557
• Publications: 5 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

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.1030-16096A>G		intron	N/A	NP_002240.3
	KCNN3	NM_001204087.2		c.1030-16096A>G		intron	N/A	NP_001191016.1	A0A087WYJ0
	KCNN3	NM_001365837.1		c.91-16096A>G		intron	N/A	NP_001352766.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNN3	ENST00000271915.9	TSL:1 MANE Select	c.1030-16096A>G		intron	N/A	ENSP00000271915.3	Q9UGI6-1
	KCNN3	ENST00000361147.8	TSL:1	c.115-16096A>G		intron	N/A	ENSP00000354764.4	Q9UGI6-2
	KCNN3	ENST00000358505.2	TSL:1	c.91-16096A>G		intron	N/A	ENSP00000351295.2	Q9UGI6-3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39312 AN: 152006 Hom.: 5694 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.285

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.258 AC: 39307 AN: 152124 Hom.: 5692 Cov.: 32 AF XY: 0.264 AC XY: 19622 AN XY: 74350

African (AFR) AF: 0.160 AC: 6625 AN: 41506

American (AMR) AF: 0.236 AC: 3605 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1541 AN: 3470

East Asian (EAS) AF: 0.137 AC: 711 AN: 5184

South Asian (SAS) AF: 0.319 AC: 1536 AN: 4816

European-Finnish (FIN) AF: 0.429 AC: 4527 AN: 10558

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19907 AN: 67990

Other (OTH) AF: 0.283 AC: 597 AN: 2106

Alfa AF: 0.272 Hom.: 16025

Bravo AF: 0.234

Asia WGS AF: 0.206 AC: 714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.79
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11584635; hg19: chr1-154760965;