Variant 1-154869723-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT-GGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_002249.6(KCNN3):c.241_242insAGC(p.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 0.021 ( 52 hom., cov: 0)

Exomes 𝑓: 0.011 ( 16 hom. )

Failed GnomAD Quality Control

Consequence

KCNN3
NM_002249.6 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.12

Variant links:

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]

KCNN3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 1-154869723-G-GGCT is Benign according to our data. Variant chr1-154869723-G-GGCT is described in ClinVar as [Benign]. Clinvar id is 1685458.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0211 (2978/141352) while in subpopulation AFR AF= 0.0451 (1705/37826). AF 95% confidence interval is 0.0433. There are 52 homozygotes in gnomad4. There are 1409 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2978 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNN3	NM_002249.6 linkuse as main transcript	c.241_242insAGC	p.Gln80dup	inframe_insertion	1/8	ENST00000271915.9
KCNN3	NM_001204087.2 linkuse as main transcript	c.241_242insAGC	p.Gln80dup	inframe_insertion	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNN3	ENST00000271915.9 linkuse as main transcript	c.241_242insAGC	p.Gln80dup	inframe_insertion	1/8	1	NM_002249.6	P1	Q9UGI6-1
KCNN3	ENST00000618040.4 linkuse as main transcript	c.241_242insAGC	p.Gln80dup	inframe_insertion	1/9	5

Frequencies

GnomAD3 genomes

AF:

0.0210

AC:

2973

AN:

141252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0451

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.0145

Gnomad EAS

AF:

0.00691

Gnomad SAS

AF:

0.0240

Gnomad FIN

AF:

0.0113

Gnomad MID

AF:

0.0232

Gnomad NFE

AF:

0.00980

Gnomad OTH

AF:

0.0133

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0105

AC:

14325

AN:

1363626

Hom.:

Cov.:

112

AF XY:

0.0108

AC XY:

7251

AN XY:

674126

show subpopulations

Gnomad4 AFR exome

AF:

0.0445

Gnomad4 AMR exome

AF:

0.0105

Gnomad4 ASJ exome

AF:

0.0147

Gnomad4 EAS exome

AF:

0.00568

Gnomad4 SAS exome

AF:

0.0222

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.00848

Gnomad4 OTH exome

AF:

0.0141

GnomAD4 genome

AF:

0.0211

AC:

2978

AN:

141352

Hom.:

Cov.:

AF XY:

0.0207

AC XY:

1409

AN XY:

68000

show subpopulations

Gnomad4 AFR

AF:

0.0451

Gnomad4 AMR

AF:

0.0225

Gnomad4 ASJ

AF:

0.0145

Gnomad4 EAS

AF:

0.00694

Gnomad4 SAS

AF:

0.0245

Gnomad4 FIN

AF:

0.0113

Gnomad4 NFE

AF:

0.00979

Gnomad4 OTH

AF:

0.0137

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over