rs1061122

Variant names:

• chr1-154859814-C-T
• rs1061122
• ENST00000361147.8:c.-102G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000361147.8(KCNN3):​c.-102G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,612,166 control chromosomes in the GnomAD database, including 42,768 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (6422 hom., cov: 33)
  • Exomes 𝑓: 0.21 (36346 hom.)
• Consequence: KCNN3 ENST00000361147.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.39
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• Zimmermann-Laband syndrome 3

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Zimmermann-Laband syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.933+9218G>A		intron_variant	Intron 1 of 7	ENST00000271915.9	NP_002240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNN3	ENST00000361147.8	c.-102G>A		5_prime_UTR_variant	Exon 1 of 8	1		ENSP00000354764.4
KCNN3	ENST00000271915.9	c.933+9218G>A		intron_variant	Intron 1 of 7	1	NM_002249.6	ENSP00000271915.3
KCNN3	ENST00000358505.2	c.-7+8135G>A		intron_variant	Intron 1 of 7	1		ENSP00000351295.2
KCNN3	ENST00000618040.4	c.933+9218G>A		intron_variant	Intron 1 of 8	5		ENSP00000481848.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40720 AN: 152052 Hom.: 6418 Cov.: 33

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.00923

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.214 AC: 313144 AN: 1459996 Hom.: 36346 Cov.: 32 AF XY: 0.212 AC XY: 153926 AN XY: 726312

African (AFR) AF: 0.436 AC: 14593 AN: 33446

American (AMR) AF: 0.136 AC: 6042 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 6618 AN: 26102

East Asian (EAS) AF: 0.00552 AC: 219 AN: 39674

South Asian (SAS) AF: 0.132 AC: 11376 AN: 86130

European-Finnish (FIN) AF: 0.198 AC: 10513 AN: 53178

Middle Eastern (MID) AF: 0.241 AC: 1387 AN: 5754

European-Non Finnish (NFE) AF: 0.225 AC: 249463 AN: 1110792

Other (OTH) AF: 0.214 AC: 12933 AN: 60330

GnomAD4 genome AF: 0.268 AC: 40745 AN: 152170 Hom.: 6422 Cov.: 33 AF XY: 0.259 AC XY: 19252 AN XY: 74422

African (AFR) AF: 0.430 AC: 17816 AN: 41478

American (AMR) AF: 0.191 AC: 2917 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 927 AN: 3470

East Asian (EAS) AF: 0.00963 AC: 50 AN: 5190

South Asian (SAS) AF: 0.127 AC: 614 AN: 4830

European-Finnish (FIN) AF: 0.198 AC: 2105 AN: 10610

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15415 AN: 67972

Other (OTH) AF: 0.238 AC: 504 AN: 2114

Alfa AF: 0.238 Hom.: 19787

Bravo AF: 0.273

Asia WGS AF: 0.0710 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.012
DANN	Benign	0.65
PhyloP100		-3.4
PromoterAI		0.028	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1061122; hg19: chr1-154832290; COSMIC: COSV55215271;