chr1-154797663-G-T

Variant names:

• chr1-154797663-G-T
• rs954785
• NM_002249.6:c.1029+24426C>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.1029+24426C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,156 control chromosomes in the GnomAD database, including 47,842 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 0.79 (47842 hom., cov: 32)
• Consequence: KCNN3 NM_002249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.1029+24426C>A		intron_variant	Intron 2 of 7	ENST00000271915.9	NP_002240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNN3	ENST00000271915.9	c.1029+24426C>A		intron_variant	Intron 2 of 7	1	NM_002249.6	ENSP00000271915.3
KCNN3	ENST00000361147.8	c.114+24426C>A		intron_variant	Intron 2 of 7	1		ENSP00000354764.4
KCNN3	ENST00000358505.2	c.90+24426C>A		intron_variant	Intron 2 of 7	1		ENSP00000351295.2
KCNN3	ENST00000618040.4	c.1029+24426C>A		intron_variant	Intron 2 of 8	5		ENSP00000481848.1

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120219 AN: 152038 Hom.: 47813 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.791 AC: 120300 AN: 152156 Hom.: 47842 Cov.: 32 AF XY: 0.797 AC XY: 59278 AN XY: 74368

African (AFR) AF: 0.743 AC: 30833 AN: 41494

American (AMR) AF: 0.840 AC: 12837 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2574 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5150 AN: 5188

South Asian (SAS) AF: 0.879 AC: 4237 AN: 4822

European-Finnish (FIN) AF: 0.842 AC: 8917 AN: 10588

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53291 AN: 67994

Other (OTH) AF: 0.800 AC: 1690 AN: 2112

Alfa AF: 0.785 Hom.: 82356

Bravo AF: 0.786

Asia WGS AF: 0.903 AC: 3138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.022
DANN	Benign	0.58
PhyloP100		-1.3
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: rs954785; hg19: chr1-154770139;