1-154869723-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT

Position:

• chr1-154869723-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002249.6(KCNN3):​c.241_242insAGCAGCAGCAGCAGCAGCAGC​(p.Gln74_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 0.049 (262 hom., cov: 0)
  • Exomes 𝑓: 0.056 (2497 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 Benign. Variant got -10 ACMG points.

• BP6: Variant 1-154869723-G-GGCTGCTGCTGCTGCTGCTGCT is Benign according to our data. Variant chr1-154869723-G-GGCTGCTGCTGCTGCTGCTGCT is described in ClinVar as [Benign]. Clinvar id is 1685432.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNN3	NM_002249.6	c.241_242insAGCAGCAGCAGCAGCAGCAGC	p.Gln74_Gln80dup	inframe_insertion	1/8	ENST00000271915.9
KCNN3	NM_001204087.2	c.241_242insAGCAGCAGCAGCAGCAGCAGC	p.Gln74_Gln80dup	inframe_insertion	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNN3	ENST00000271915.9	c.241_242insAGCAGCAGCAGCAGCAGCAGC	p.Gln74_Gln80dup	inframe_insertion	1/8	1	NM_002249.6	P1
KCNN3	ENST00000618040.4	c.241_242insAGCAGCAGCAGCAGCAGCAGC	p.Gln74_Gln80dup	inframe_insertion	1/9	5

Frequencies

GnomAD3 genomes AF: 0.0491 AC: 6935 AN: 141176 Hom.: 261 Cov.: 0

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.0326

Gnomad ASJ AF: 0.0264

Gnomad EAS AF: 0.0493

Gnomad SAS AF: 0.0383

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.0298

Gnomad NFE AF: 0.0602

Gnomad OTH AF: 0.0515

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0562 AC: 76400 AN: 1358946 Hom.: 2497 Cov.: 112 AF XY: 0.0554 AC XY: 37211 AN XY: 671666

Gnomad4 AFR exome AF: 0.0426

Gnomad4 AMR exome AF: 0.0308

Gnomad4 ASJ exome AF: 0.0305

Gnomad4 EAS exome AF: 0.0369

Gnomad4 SAS exome AF: 0.0399

Gnomad4 FIN exome AF: 0.0324

Gnomad4 NFE exome AF: 0.0614

Gnomad4 OTH exome AF: 0.0508

GnomAD4 genome AF: 0.0492 AC: 6951 AN: 141278 Hom.: 262 Cov.: 0 AF XY: 0.0473 AC XY: 3212 AN XY: 67962

Gnomad4 AFR AF: 0.0410

Gnomad4 AMR AF: 0.0325

Gnomad4 ASJ AF: 0.0264

Gnomad4 EAS AF: 0.0493

Gnomad4 SAS AF: 0.0381

Gnomad4 FIN AF: 0.0314

Gnomad4 NFE AF: 0.0601

Gnomad4 OTH AF: 0.0521

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;