1-154869723-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT-GGCT

Variant summary

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

The NM_002249.6(KCNN3):c.215_241del(p.Gln72_Gln80del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000275 in 1,506,516 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00028 (0 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-GGCTGCTGCTGCTGCTGCTGCTGCTGCT-G is Benign according to our data. Variant chr1-154869723-GGCTGCTGCTGCTGCTGCTGCTGCTGCT-G is described in ClinVar as [Benign]. Clinvar id is 1685501.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 37 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNN3	NM_002249.6	c.215_241del	p.Gln72_Gln80del	inframe_deletion	1/8	ENST00000271915.9
KCNN3	NM_001204087.2	c.215_241del	p.Gln72_Gln80del	inframe_deletion	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNN3	ENST00000271915.9	c.215_241del	p.Gln72_Gln80del	inframe_deletion	1/8	1	NM_002249.6	P1
KCNN3	ENST00000618040.4	c.215_241del	p.Gln72_Gln80del	inframe_deletion	1/9	5

Frequencies

GnomAD3 genomes AF: 0.000262 AC: 37 AN: 141288 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000424

Gnomad ASJ AF: 0.00148

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000494

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00331

Gnomad NFE AF: 0.000322

Gnomad OTH AF: 0.000531

GnomAD4 exome AF: 0.000277 AC: 378 AN: 1365126 Hom.: 0 AF XY: 0.000282 AC XY: 190 AN XY: 674886

Gnomad4 AFR exome AF: 0.0000321

Gnomad4 AMR exome AF: 0.000282

Gnomad4 ASJ exome AF: 0.000601

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000267

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000271

Gnomad4 OTH exome AF: 0.000651

GnomAD4 genome AF: 0.000262 AC: 37 AN: 141390 Hom.: 0 Cov.: 0 AF XY: 0.000235 AC XY: 16 AN XY: 68016

Gnomad4 AFR AF: 0.0000264

Gnomad4 AMR AF: 0.000424

Gnomad4 ASJ AF: 0.00148

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000495

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000322

Gnomad4 OTH AF: 0.000526

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;