1-154869723-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT-GGCTGCTGCTGCT

Position:

• chr1-154869723-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT-GGCTGCTGCTGCT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_002249.6(KCNN3):​c.224_241del​(p.Gln75_Gln80del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000611 in 1,506,512 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000071 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000060 (1 hom.)
• Consequence: KCNN3 NM_002249.6 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.39

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-154869723-GGCTGCTGCTGCTGCTGCT-G is Benign according to our data. Variant chr1-154869723-GGCTGCTGCTGCTGCTGCT-G is described in ClinVar as [Benign]. Clinvar id is 1685442.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNN3	NM_002249.6	c.224_241del	p.Gln75_Gln80del	inframe_deletion	1/8	ENST00000271915.9
KCNN3	NM_001204087.2	c.224_241del	p.Gln75_Gln80del	inframe_deletion	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNN3	ENST00000271915.9	c.224_241del	p.Gln75_Gln80del	inframe_deletion	1/8	1	NM_002249.6	P1
KCNN3	ENST00000618040.4	c.224_241del	p.Gln75_Gln80del	inframe_deletion	1/9	5

Frequencies

GnomAD3 genomes AF: 0.0000708 AC: 10 AN: 141286 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000988

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000307

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000601 AC: 82 AN: 1365124 Hom.: 1 AF XY: 0.0000682 AC XY: 46 AN XY: 674886

Gnomad4 AFR exome AF: 0.0000321

Gnomad4 AMR exome AF: 0.0000563

Gnomad4 ASJ exome AF: 0.0000401

Gnomad4 EAS exome AF: 0.0000281

Gnomad4 SAS exome AF: 0.000279

Gnomad4 FIN exome AF: 0.0000433

Gnomad4 NFE exome AF: 0.0000447

Gnomad4 OTH exome AF: 0.0000352

GnomAD4 genome AF: 0.0000707 AC: 10 AN: 141388 Hom.: 0 Cov.: 0 AF XY: 0.0000735 AC XY: 5 AN XY: 68016

Gnomad4 AFR AF: 0.000106

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000990

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000307

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3831942; hg19: chr1-154842199;