rs4845396

Variant names:

• chr1-154855933-G-A
• rs4845396
• NM_002249.6:c.933+13099C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-154855933-G-A
• chr1-154855933-G-T

Variant summary

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

The NM_002249.6(KCNN3):​c.933+13099C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,022 control chromosomes in the GnomAD database, including 19,588 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 0.48 (19588 hom., cov: 31)
• Consequence: KCNN3 NM_002249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 10 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: 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNN3	NM_002249.6	MANE Select	c.933+13099C>T		intron	N/A	NP_002240.3
	KCNN3	NM_001204087.2		c.933+13099C>T		intron	N/A	NP_001191016.1
	KCNN3	NM_001365837.1		c.-7+12016C>T		intron	N/A	NP_001352766.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNN3	ENST00000271915.9	TSL:1 MANE Select	c.933+13099C>T		intron	N/A	ENSP00000271915.3
	KCNN3	ENST00000361147.8	TSL:1	c.18+3762C>T		intron	N/A	ENSP00000354764.4
	KCNN3	ENST00000358505.2	TSL:1	c.-7+12016C>T		intron	N/A	ENSP00000351295.2

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72690 AN: 151904 Hom.: 19573 Cov.: 31

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.478 AC: 72740 AN: 152022 Hom.: 19588 Cov.: 31 AF XY: 0.493 AC XY: 36597 AN XY: 74304

African (AFR) AF: 0.272 AC: 11268 AN: 41478

American (AMR) AF: 0.626 AC: 9570 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2177 AN: 3468

East Asian (EAS) AF: 0.964 AC: 4996 AN: 5182

South Asian (SAS) AF: 0.730 AC: 3519 AN: 4820

European-Finnish (FIN) AF: 0.559 AC: 5895 AN: 10538

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33677 AN: 67936

Other (OTH) AF: 0.509 AC: 1074 AN: 2108

Alfa AF: 0.509 Hom.: 45448

Bravo AF: 0.476

Asia WGS AF: 0.804 AC: 2791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.72
PhyloP100		0.093
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: rs4845396; hg19: chr1-154828409; COSMIC: COSV55223558;