1-154783367-C-T

Variant names:

• chr1-154783367-C-T
• rs11589855
• NM_002249.6:c.1030-10974G>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.1030-10974G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,106 control chromosomes in the GnomAD database, including 10,248 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 0.36 (10248 hom., cov: 32)
• Consequence: KCNN3 NM_002249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873
• Publications: 4 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 (NFE) allele frequency at 95% confidence interval = 0.386 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.1030-10974G>A		intron	N/A	NP_002240.3
	KCNN3	NM_001204087.2		c.1030-10974G>A		intron	N/A	NP_001191016.1
	KCNN3	NM_001365837.1		c.91-10974G>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.1030-10974G>A		intron	N/A	ENSP00000271915.3
	KCNN3	ENST00000361147.8	TSL:1	c.115-10974G>A		intron	N/A	ENSP00000354764.4
	KCNN3	ENST00000358505.2	TSL:1	c.91-10974G>A		intron	N/A	ENSP00000351295.2

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54519 AN: 151988 Hom.: 10244 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.358 AC: 54530 AN: 152106 Hom.: 10248 Cov.: 32 AF XY: 0.364 AC XY: 27074 AN XY: 74334

African (AFR) AF: 0.271 AC: 11258 AN: 41498

American (AMR) AF: 0.325 AC: 4973 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1959 AN: 3470

East Asian (EAS) AF: 0.345 AC: 1781 AN: 5168

South Asian (SAS) AF: 0.362 AC: 1746 AN: 4824

European-Finnish (FIN) AF: 0.488 AC: 5142 AN: 10546

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26495 AN: 67984

Other (OTH) AF: 0.384 AC: 811 AN: 2114

Alfa AF: 0.376 Hom.: 19062

Bravo AF: 0.340

Asia WGS AF: 0.348 AC: 1212 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	0.30
DANN	Benign	0.57
PhyloP100		-0.87
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: rs11589855; hg19: chr1-154755843;