1-154707091-C-T

Variant summary

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

The NM_002249.6(KCNN3):c.*885G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,196 control chromosomes in the GnomAD database, including 57,950 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 0.87 (57949 hom., cov: 32)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: KCNN3 NM_002249.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNN3	NM_002249.6	c.*885G>A		3_prime_UTR_variant	8/8	ENST00000271915.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNN3	ENST00000271915.9	c.*885G>A		3_prime_UTR_variant	8/8	1	NM_002249.6	P1
KCNN3	ENST00000618040.4	c.*885G>A		3_prime_UTR_variant	9/9	5
KCNN3	ENST00000515643.1	n.305+585G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132302 AN: 152074 Hom.: 57914 Cov.: 32

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.884

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.750

GnomAD4 genome AF: 0.870 AC: 132392 AN: 152192 Hom.: 57949 Cov.: 32 AF XY: 0.873 AC XY: 64991 AN XY: 74408

Gnomad4 AFR AF: 0.763

Gnomad4 AMR AF: 0.906

Gnomad4 ASJ AF: 0.924

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.947

Gnomad4 FIN AF: 0.927

Gnomad4 NFE AF: 0.901

Gnomad4 OTH AF: 0.883

Alfa AF: 0.898 Hom.: 35442

Bravo AF: 0.864

Asia WGS AF: 0.933 AC: 3244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	5.0
Dann	Benign	0.64

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: rs1995662; hg19: chr1-154679567;