rs6691316

Variant names:

• chr1-154781718-C-T
• rs6691316
• NM_002249.6:c.1030-9325G>A

Variant summary

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

The NM_002249.6(KCNN3):​c.1030-9325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,080 control chromosomes in the GnomAD database, including 33,682 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 0.66 (33682 hom., cov: 32)
• Consequence: KCNN3 NM_002249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 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.1030-9325G>A		intron	N/A	NP_002240.3
	KCNN3	NM_001204087.2		c.1030-9325G>A		intron	N/A	NP_001191016.1
	KCNN3	NM_001365837.1		c.91-9325G>A		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.1030-9325G>A		intron	N/A	ENSP00000271915.3
	KCNN3	ENST00000361147.8	TSL:1	c.115-9325G>A		intron	N/A	ENSP00000354764.4
	KCNN3	ENST00000358505.2	TSL:1	c.91-9325G>A		intron	N/A	ENSP00000351295.2

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100945 AN: 151962 Hom.: 33650 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.664 AC: 101022 AN: 152080 Hom.: 33682 Cov.: 32 AF XY: 0.668 AC XY: 49691 AN XY: 74340

African (AFR) AF: 0.629 AC: 26100 AN: 41462

American (AMR) AF: 0.687 AC: 10505 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2545 AN: 3470

East Asian (EAS) AF: 0.784 AC: 4057 AN: 5176

South Asian (SAS) AF: 0.688 AC: 3312 AN: 4812

European-Finnish (FIN) AF: 0.722 AC: 7637 AN: 10574

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44719 AN: 67978

Other (OTH) AF: 0.672 AC: 1419 AN: 2112

Alfa AF: 0.660 Hom.: 73981

Bravo AF: 0.660

Asia WGS AF: 0.730 AC: 2539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.6
DANN	Benign	0.46
PhyloP100		-0.095
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: rs6691316; hg19: chr1-154754194;