chr1-154852794-T-G

Variant names:

• chr1-154852794-T-G
• rs11264275
• NM_002249.6:c.933+16238A>C

Variant summary

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

The NM_002249.6(KCNN3):​c.933+16238A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 151,996 control chromosomes in the GnomAD database, including 19,122 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 0.47 (19122 hom., cov: 32)
• Consequence: KCNN3 NM_002249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.593
• Publications: 8 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNN3	NM_002249.6	MANE Select	c.933+16238A>C		intron	N/A	NP_002240.3
	KCNN3	NM_001204087.2		c.933+16238A>C		intron	N/A	NP_001191016.1	A0A087WYJ0
	KCNN3	NM_001365837.1		c.-7+15155A>C		intron	N/A	NP_001352766.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNN3	ENST00000271915.9	TSL:1 MANE Select	c.933+16238A>C		intron	N/A	ENSP00000271915.3	Q9UGI6-1
	KCNN3	ENST00000361147.8	TSL:1	c.18+6901A>C		intron	N/A	ENSP00000354764.4	Q9UGI6-2
	KCNN3	ENST00000358505.2	TSL:1	c.-7+15155A>C		intron	N/A	ENSP00000351295.2	Q9UGI6-3

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71526 AN: 151878 Hom.: 19108 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.471 AC: 71571 AN: 151996 Hom.: 19122 Cov.: 32 AF XY: 0.486 AC XY: 36109 AN XY: 74258

African (AFR) AF: 0.258 AC: 10682 AN: 41464

American (AMR) AF: 0.614 AC: 9363 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1999 AN: 3472

East Asian (EAS) AF: 0.964 AC: 4986 AN: 5170

South Asian (SAS) AF: 0.731 AC: 3514 AN: 4810

European-Finnish (FIN) AF: 0.581 AC: 6137 AN: 10560

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33267 AN: 67954

Other (OTH) AF: 0.503 AC: 1062 AN: 2110

Alfa AF: 0.491 Hom.: 72064

Bravo AF: 0.467

Asia WGS AF: 0.807 AC: 2801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.50
PhyloP100		0.59
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: rs11264275; hg19: chr1-154825270;