chr1-154859846-A-C

Position:

• chr1-154859846-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_170782.3(KCNN3):​c.-134T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.967 in 1,600,466 control chromosomes in the GnomAD database, including 748,599 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 0.96 (69930 hom., cov: 34)
  • Exomes 𝑓: 0.97 (678669 hom.)
• Consequence: KCNN3 NM_170782.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.933+9186T>G		intron_variant		ENST00000271915.9	NP_002240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN3	ENST00000271915.9	c.933+9186T>G		intron_variant		1	NM_002249.6	ENSP00000271915.3
KCNN3	ENST00000358505.2	c.-7+8103T>G		intron_variant		1		ENSP00000351295.2
KCNN3	ENST00000618040.4	c.933+9186T>G		intron_variant		5		ENSP00000481848.1
KCNN3	ENST00000361147.8	c.-134T>G		upstream_gene_variant		1		ENSP00000354764.4

Frequencies

GnomAD3 genomes AF: 0.958 AC: 145801 AN: 152210 Hom.: 69876 Cov.: 34

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.959

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.945

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.952

GnomAD4 exome AF: 0.968 AC: 1401869 AN: 1448138 Hom.: 678669 Cov.: 33 AF XY: 0.967 AC XY: 695903 AN XY: 719650

Gnomad4 AFR exome AF: 0.921

Gnomad4 AMR exome AF: 0.975

Gnomad4 ASJ exome AF: 0.949

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.948

Gnomad4 FIN exome AF: 0.985

Gnomad4 NFE exome AF: 0.970

Gnomad4 OTH exome AF: 0.962

GnomAD4 genome AF: 0.958 AC: 145914 AN: 152328 Hom.: 69930 Cov.: 34 AF XY: 0.959 AC XY: 71450 AN XY: 74492

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.961

Gnomad4 ASJ AF: 0.945

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.948

Gnomad4 FIN AF: 0.986

Gnomad4 NFE AF: 0.969

Gnomad4 OTH AF: 0.952

Alfa AF: 0.964 Hom.: 25180

Bravo AF: 0.954

Asia WGS AF: 0.976 AC: 3395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1218586; hg19: chr1-154832322;