rs17719880

Variant names:

• chr1-154819455-A-G
• rs17719880
• NM_002249.6:c.1029+2634T>C

Variant summary

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

The NM_002249.6(KCNN3):​c.1029+2634T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,100 control chromosomes in the GnomAD database, including 4,067 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 0.22 (4067 hom., cov: 32)
• Consequence: KCNN3 NM_002249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 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.1029+2634T>C		intron	N/A	NP_002240.3
	KCNN3	NM_001204087.2		c.1029+2634T>C		intron	N/A	NP_001191016.1
	KCNN3	NM_001365837.1		c.90+2634T>C		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.1029+2634T>C		intron	N/A	ENSP00000271915.3
	KCNN3	ENST00000361147.8	TSL:1	c.114+2634T>C		intron	N/A	ENSP00000354764.4
	KCNN3	ENST00000358505.2	TSL:1	c.90+2634T>C		intron	N/A	ENSP00000351295.2

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33946 AN: 151982 Hom.: 4060 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0855

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.223 AC: 33976 AN: 152100 Hom.: 4067 Cov.: 32 AF XY: 0.220 AC XY: 16323 AN XY: 74344

African (AFR) AF: 0.294 AC: 12188 AN: 41468

American (AMR) AF: 0.151 AC: 2314 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3472

East Asian (EAS) AF: 0.113 AC: 585 AN: 5178

South Asian (SAS) AF: 0.0851 AC: 410 AN: 4816

European-Finnish (FIN) AF: 0.202 AC: 2132 AN: 10574

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15245 AN: 67978

Other (OTH) AF: 0.185 AC: 391 AN: 2112

Alfa AF: 0.216 Hom.: 1271

Bravo AF: 0.222

Asia WGS AF: 0.113 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.51
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17719880; hg19: chr1-154791931;