Variant chr1-154869723-G-GGCTGCTGCTGCTGCT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_002249.6(KCNN3):c.241_242insAGCAGCAGCAGCAGC(p.Gln76_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 0.30 ( 7510 hom., cov: 0)

Exomes 𝑓: 0.29 ( 19618 hom. )

Failed GnomAD Quality Control

Consequence

KCNN3
NM_002249.6 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-154869723-G-GGCTGCTGCTGCTGCT is Benign according to our data. Variant chr1-154869723-G-GGCTGCTGCTGCTGCT is described in ClinVar as [Benign]. Clinvar id is 1290509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN3	NM_002249.6 linkuse as main transcript	c.241_242insAGCAGCAGCAGCAGC	p.Gln76_Gln80dup	inframe_insertion	1/8	ENST00000271915.9	NP_002240.3
KCNN3	NM_001204087.2 linkuse as main transcript	c.241_242insAGCAGCAGCAGCAGC	p.Gln76_Gln80dup	inframe_insertion	1/9		NP_001191016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN3	ENST00000271915.9 linkuse as main transcript	c.241_242insAGCAGCAGCAGCAGC	p.Gln76_Gln80dup	inframe_insertion	1/8	1	NM_002249.6	ENSP00000271915	P1	Q9UGI6-1
KCNN3	ENST00000618040.4 linkuse as main transcript	c.241_242insAGCAGCAGCAGCAGC	p.Gln76_Gln80dup	inframe_insertion	1/9	5		ENSP00000481848

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

42429

AN:

140906

Hom.:

7505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.447

Gnomad ASJ

AF:

0.456

Gnomad EAS

AF:

0.496

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.324

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.292

AC:

391526

AN:

1341996

Hom.:

19618

Cov.:

112

AF XY:

0.292

AC XY:

193574

AN XY:

663426

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.391

Gnomad4 ASJ exome

AF:

0.355

Gnomad4 EAS exome

AF:

0.392

Gnomad4 SAS exome

AF:

0.282

Gnomad4 FIN exome

AF:

0.265

Gnomad4 NFE exome

AF:

0.290

Gnomad4 OTH exome

AF:

0.299

GnomAD4 genome

AF:

0.301

AC:

42440

AN:

141008

Hom.:

7510

Cov.:

AF XY:

0.302

AC XY:

20519

AN XY:

67850

show subpopulations

Gnomad4 AFR

AF:

0.138

Gnomad4 AMR

AF:

0.448

Gnomad4 ASJ

AF:

0.456

Gnomad4 EAS

AF:

0.496

Gnomad4 SAS

AF:

0.330

Gnomad4 FIN

AF:

0.300

Gnomad4 NFE

AF:

0.341

Gnomad4 OTH

AF:

0.322

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 25, 2020

- -

Zimmermann-laband syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 11, 2021

- -

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