chr1-154869723-GGCTGCTGCT-G

Position:

• chr1-154869723-GGCTGCTGCT-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_002249.6(KCNN3):​c.233_241del​(p.Gln78_Gln80del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,506,444 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0013 (2 hom.)
• Consequence: KCNN3 NM_002249.6 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.12

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 Benign. Variant got -12 ACMG points.

• BP6: Variant 1-154869723-GGCTGCTGCT-G is Benign according to our data. Variant chr1-154869723-GGCTGCTGCT-G is described in ClinVar as [Likely_benign]. Clinvar id is 1685424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 359 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.233_241del	p.Gln78_Gln80del	inframe_deletion	1/8	ENST00000271915.9	NP_002240.3
KCNN3	NM_001204087.2	c.233_241del	p.Gln78_Gln80del	inframe_deletion	1/9		NP_001191016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN3	ENST00000271915.9	c.233_241del	p.Gln78_Gln80del	inframe_deletion	1/8	1	NM_002249.6	ENSP00000271915	P1
KCNN3	ENST00000618040.4	c.233_241del	p.Gln78_Gln80del	inframe_deletion	1/9	5		ENSP00000481848

Frequencies

GnomAD3 genomes AF: 0.00254 AC: 359 AN: 141284 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00400

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.000707

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00475

Gnomad SAS AF: 0.00247

Gnomad FIN AF: 0.00855

Gnomad MID AF: 0.00331

Gnomad NFE AF: 0.000936

Gnomad OTH AF: 0.00266

GnomAD4 exome AF: 0.00135 AC: 1839 AN: 1365058 Hom.: 2 AF XY: 0.00134 AC XY: 903 AN XY: 674866

Gnomad4 AFR exome AF: 0.00415

Gnomad4 AMR exome AF: 0.00130

Gnomad4 ASJ exome AF: 0.000160

Gnomad4 EAS exome AF: 0.00225

Gnomad4 SAS exome AF: 0.00160

Gnomad4 FIN exome AF: 0.00694

Gnomad4 NFE exome AF: 0.000989

Gnomad4 OTH exome AF: 0.00158

GnomAD4 genome AF: 0.00254 AC: 359 AN: 141386 Hom.: 0 Cov.: 0 AF XY: 0.00307 AC XY: 209 AN XY: 68012

Gnomad4 AFR AF: 0.00399

Gnomad4 AMR AF: 0.000706

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00477

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.00855

Gnomad4 NFE AF: 0.000936

Gnomad4 OTH AF: 0.00263

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

KCNN3: BS1 -

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;