1-154859828-T-C

Position:

• chr1-154859828-T-C

Variant summary

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

The NM_170782.3(KCNN3):​c.-116A>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 0.72 in 1,609,248 control chromosomes in the GnomAD database, including 423,479 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 0.66 (34481 hom., cov: 34)
  • Exomes 𝑓: 0.73 (388998 hom.)
• Consequence: KCNN3 NM_170782.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.933+9204A>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+9204A>G		intron_variant		1	NM_002249.6	ENSP00000271915.3

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99787 AN: 152090 Hom.: 34459 Cov.: 34

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.671

GnomAD4 exome AF: 0.727 AC: 1058903 AN: 1457040 Hom.: 388998 Cov.: 35 AF XY: 0.729 AC XY: 528072 AN XY: 724616

Gnomad4 AFR exome AF: 0.424

Gnomad4 AMR exome AF: 0.825

Gnomad4 ASJ exome AF: 0.654

Gnomad4 EAS exome AF: 0.994

Gnomad4 SAS exome AF: 0.798

Gnomad4 FIN exome AF: 0.756

Gnomad4 NFE exome AF: 0.718

Gnomad4 OTH exome AF: 0.716

GnomAD4 genome AF: 0.656 AC: 99858 AN: 152208 Hom.: 34481 Cov.: 34 AF XY: 0.667 AC XY: 49635 AN XY: 74428

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.757

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.674

Alfa AF: 0.703 Hom.: 18237

Bravo AF: 0.648

Asia WGS AF: 0.886 AC: 3077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.45
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs4845397; hg19: chr1-154832304;