rs1218553

Variant names:

• chr1-154826151-C-A
• rs1218553
• NM_002249.6:c.934-3967G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-154826151-C-A
• chr1-154826151-C-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.934-3967G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 149,784 control chromosomes in the GnomAD database, including 41,038 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 0.73 (41038 hom., cov: 29)
• Consequence: KCNN3 NM_002249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681
• 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: 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.934-3967G>T		intron_variant	Intron 1 of 7	ENST00000271915.9	NP_002240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNN3	ENST00000271915.9	c.934-3967G>T		intron_variant	Intron 1 of 7	1	NM_002249.6	ENSP00000271915.3
KCNN3	ENST00000361147.8	c.19-3967G>T		intron_variant	Intron 1 of 7	1		ENSP00000354764.4
KCNN3	ENST00000358505.2	c.-6-3967G>T		intron_variant	Intron 1 of 7	1		ENSP00000351295.2
KCNN3	ENST00000618040.4	c.934-3967G>T		intron_variant	Intron 1 of 8	5		ENSP00000481848.1

Frequencies

GnomAD3 genomes AF: 0.732 AC: 109507 AN: 149676 Hom.: 40988 Cov.: 29

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.731

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

GnomAD4 genome AF: 0.732 AC: 109608 AN: 149784 Hom.: 41038 Cov.: 29 AF XY: 0.733 AC XY: 53496 AN XY: 72996

African (AFR) AF: 0.855 AC: 34622 AN: 40480

American (AMR) AF: 0.775 AC: 11717 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2720 AN: 3456

East Asian (EAS) AF: 0.936 AC: 4778 AN: 5104

South Asian (SAS) AF: 0.770 AC: 3647 AN: 4736

European-Finnish (FIN) AF: 0.640 AC: 6459 AN: 10098

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43303 AN: 67514

Other (OTH) AF: 0.729 AC: 1517 AN: 2080

Alfa AF: 0.683 Hom.: 44336

Bravo AF: 0.750

Asia WGS AF: 0.830 AC: 2883 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.34
DANN	Benign	0.18
PhyloP100		-0.68
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: rs1218553; hg19: chr1-154798627;