NM_002249.6:c.227_241delAGCAGCAGCAGCAGC

Variant names:

• chr1-154869722-TGGCTGCTGCTGCTGC-TG
• NM_002249.6:c.228_241delGCAGCAGCAGCAGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002249.6(KCNN3):​c.228_241delGCAGCAGCAGCAGC​(p.Gln76HisfsTer54) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 0)
• Consequence: KCNN3 NM_002249.6 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.39
• Publications: 0 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: G2P, Ambry Genetics, 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)

ENSG00000308854 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.228_241delGCAGCAGCAGCAGC	p.Gln76HisfsTer54	frameshift	Exon 1 of 8	NP_002240.3
	KCNN3	NM_001204087.2		c.228_241delGCAGCAGCAGCAGC	p.Gln76HisfsTer54	frameshift	Exon 1 of 9	NP_001191016.1	A0A087WYJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNN3	ENST00000271915.9	TSL:1 MANE Select	c.228_241delGCAGCAGCAGCAGC	p.Gln76HisfsTer54	frameshift	Exon 1 of 8	ENSP00000271915.3	Q9UGI6-1
	KCNN3	ENST00000618040.4	TSL:5	c.228_241delGCAGCAGCAGCAGC	p.Gln76HisfsTer54	frameshift	Exon 1 of 9	ENSP00000481848.1	A0A087WYJ0
	KCNN3	ENST00000874071.1		c.228_241delGCAGCAGCAGCAGC	p.Gln76HisfsTer54	frameshift	Exon 1 of 7	ENSP00000544130.1

Frequencies

GnomAD3 genomes Cov.: 0

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

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-154842198;