chr1-154869723-GGCTGCTGCTGCTGCT-G

Position:

• chr1-154869723-GGCTGCTGCTGCTGCT-G

Variant summary

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

The NM_002249.6(KCNN3):​c.227_241del​(p.Gln76_Gln80del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000295 in 1,506,508 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00050 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00027 (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-GGCTGCTGCTGCTGCT-G is Benign according to our data. Variant chr1-154869723-GGCTGCTGCTGCTGCT-G is described in ClinVar as [Benign]. Clinvar id is 1685505.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 71 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.227_241del	p.Gln76_Gln80del	inframe_deletion	1/8	ENST00000271915.9	NP_002240.3
KCNN3	NM_001204087.2	c.227_241del	p.Gln76_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.227_241del	p.Gln76_Gln80del	inframe_deletion	1/8	1	NM_002249.6	ENSP00000271915	P1
KCNN3	ENST00000618040.4	c.227_241del	p.Gln76_Gln80del	inframe_deletion	1/9	5		ENSP00000481848

Frequencies

GnomAD3 genomes AF: 0.000503 AC: 71 AN: 141288 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000954

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000212

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000648

Gnomad SAS AF: 0.000988

Gnomad FIN AF: 0.000110

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000273 AC: 373 AN: 1365118 Hom.: 1 AF XY: 0.000277 AC XY: 187 AN XY: 674884

Gnomad4 AFR exome AF: 0.000289

Gnomad4 AMR exome AF: 0.0000563

Gnomad4 ASJ exome AF: 0.000120

Gnomad4 EAS exome AF: 0.000365

Gnomad4 SAS exome AF: 0.000406

Gnomad4 FIN exome AF: 0.0000217

Gnomad4 NFE exome AF: 0.000277

Gnomad4 OTH exome AF: 0.000370

GnomAD4 genome AF: 0.000502 AC: 71 AN: 141390 Hom.: 0 Cov.: 0 AF XY: 0.000588 AC XY: 40 AN XY: 68016

Gnomad4 AFR AF: 0.000951

Gnomad4 AMR AF: 0.000212

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000650

Gnomad4 SAS AF: 0.000990

Gnomad4 FIN AF: 0.000110

Gnomad4 NFE AF: 0.000368

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;