chr1-154778340-C-A

Variant names:

• chr1-154778340-C-A
• rs7532286
• NM_002249.6:c.1030-5947G>T

Variant summary

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

The NM_002249.6(KCNN3):​c.1030-5947G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,034 control chromosomes in the GnomAD database, including 20,776 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 0.51 (20776 hom., cov: 32)
• Consequence: KCNN3 NM_002249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.1030-5947G>T		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.1030-5947G>T		intron_variant	Intron 2 of 7	1	NM_002249.6	ENSP00000271915.3
KCNN3	ENST00000361147.8	c.115-5947G>T		intron_variant	Intron 2 of 7	1		ENSP00000354764.4
KCNN3	ENST00000358505.2	c.91-5947G>T		intron_variant	Intron 2 of 7	1		ENSP00000351295.2
KCNN3	ENST00000618040.4	c.1030-5947G>T		intron_variant	Intron 2 of 8	5		ENSP00000481848.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77814 AN: 151918 Hom.: 20734 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.512 AC: 77901 AN: 152034 Hom.: 20776 Cov.: 32 AF XY: 0.510 AC XY: 37901 AN XY: 74298

African (AFR) AF: 0.655 AC: 27178 AN: 41464

American (AMR) AF: 0.412 AC: 6295 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2168 AN: 3466

East Asian (EAS) AF: 0.311 AC: 1612 AN: 5176

South Asian (SAS) AF: 0.404 AC: 1949 AN: 4822

European-Finnish (FIN) AF: 0.505 AC: 5318 AN: 10540

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31702 AN: 67980

Other (OTH) AF: 0.510 AC: 1076 AN: 2108

Alfa AF: 0.479 Hom.: 33781

Bravo AF: 0.510

Asia WGS AF: 0.395 AC: 1375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.80
DANN	Benign	0.22
PhyloP100		-0.12
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: rs7532286; hg19: chr1-154750816;