chr1-154869723-G-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT

Position:

• chr1-154869723-G-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT

Variant summary

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

The NM_002249.6(KCNN3):​c.241_242insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC​(p.Gln71_Gln80dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (4 hom., cov: 0)
  • Exomes 𝑓: 0.00048 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNN3 NM_002249.6 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-154869723-G-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT is Benign according to our data. Variant chr1-154869723-G-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT is described in ClinVar as [Benign]. Clinvar id is 1685494.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 389 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.241_242insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC	p.Gln71_Gln80dup	inframe_insertion	1/8	ENST00000271915.9	NP_002240.3
KCNN3	NM_001204087.2	c.241_242insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC	p.Gln71_Gln80dup	inframe_insertion	1/9		NP_001191016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN3	ENST00000271915.9	c.241_242insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC	p.Gln71_Gln80dup	inframe_insertion	1/8	1	NM_002249.6	ENSP00000271915	P1
KCNN3	ENST00000618040.4	c.241_242insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC	p.Gln71_Gln80dup	inframe_insertion	1/9	5		ENSP00000481848

Frequencies

GnomAD3 genomes AF: 0.00272 AC: 384 AN: 141268 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.00666

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000849

Gnomad ASJ AF: 0.000296

Gnomad EAS AF: 0.00259

Gnomad SAS AF: 0.00346

Gnomad FIN AF: 0.000439

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00133

Gnomad OTH AF: 0.00159

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000484 AC: 661 AN: 1365104 Hom.: 1 Cov.: 112 AF XY: 0.000507 AC XY: 342 AN XY: 674866

Gnomad4 AFR exome AF: 0.00302

Gnomad4 AMR exome AF: 0.000535

Gnomad4 ASJ exome AF: 0.000160

Gnomad4 EAS exome AF: 0.00163

Gnomad4 SAS exome AF: 0.00100

Gnomad4 FIN exome AF: 0.000303

Gnomad4 NFE exome AF: 0.000341

Gnomad4 OTH exome AF: 0.000528

GnomAD4 genome AF: 0.00275 AC: 389 AN: 141370 Hom.: 4 Cov.: 0 AF XY: 0.00291 AC XY: 198 AN XY: 68000

Gnomad4 AFR AF: 0.00677

Gnomad4 AMR AF: 0.000848

Gnomad4 ASJ AF: 0.000296

Gnomad4 EAS AF: 0.00260

Gnomad4 SAS AF: 0.00346

Gnomad4 FIN AF: 0.000439

Gnomad4 NFE AF: 0.00133

Gnomad4 OTH AF: 0.00158

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;