chr1-154869723-GGCTGCT-G

Position:

• chr1-154869723-GGCTGCT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002249.6(KCNN3):​c.236_241del​(p.Gln79_Gln80del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,504,596 control chromosomes in the GnomAD database, including 42 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (36 hom., cov: 0)
  • Exomes 𝑓: 0.0022 (6 hom.)
• Consequence: KCNN3 NM_002249.6 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.12

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 -10 ACMG points.

• BP6: Variant 1-154869723-GGCTGCT-G is Benign according to our data. Variant chr1-154869723-GGCTGCT-G is described in ClinVar as [Benign]. Clinvar id is 1685389.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0125 (1767/141370) while in subpopulation AFR AF= 0.0411 (1553/37824). AF 95% confidence interval is 0.0394. There are 36 homozygotes in gnomad4. There are 805 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1767 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.236_241del	p.Gln79_Gln80del	inframe_deletion	1/8	ENST00000271915.9	NP_002240.3
KCNN3	NM_001204087.2	c.236_241del	p.Gln79_Gln80del	inframe_deletion	1/9		NP_001191016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN3	ENST00000271915.9	c.236_241del	p.Gln79_Gln80del	inframe_deletion	1/8	1	NM_002249.6	ENSP00000271915	P1
KCNN3	ENST00000618040.4	c.236_241del	p.Gln79_Gln80del	inframe_deletion	1/9	5		ENSP00000481848

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1765 AN: 141268 Hom.: 36 Cov.: 0

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00743

Gnomad ASJ AF: 0.00474

Gnomad EAS AF: 0.00130

Gnomad SAS AF: 0.00321

Gnomad FIN AF: 0.000548

Gnomad MID AF: 0.0199

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.00903

GnomAD4 exome AF: 0.00219 AC: 2982 AN: 1363226 Hom.: 6 AF XY: 0.00217 AC XY: 1465 AN XY: 673940

Gnomad4 AFR exome AF: 0.0427

Gnomad4 AMR exome AF: 0.00403

Gnomad4 ASJ exome AF: 0.00473

Gnomad4 EAS exome AF: 0.00101

Gnomad4 SAS exome AF: 0.00419

Gnomad4 FIN exome AF: 0.000347

Gnomad4 NFE exome AF: 0.000728

Gnomad4 OTH exome AF: 0.00386

GnomAD4 genome AF: 0.0125 AC: 1767 AN: 141370 Hom.: 36 Cov.: 0 AF XY: 0.0118 AC XY: 805 AN XY: 68002

Gnomad4 AFR AF: 0.0411

Gnomad4 AMR AF: 0.00742

Gnomad4 ASJ AF: 0.00474

Gnomad4 EAS AF: 0.00130

Gnomad4 SAS AF: 0.00322

Gnomad4 FIN AF: 0.000548

Gnomad4 NFE AF: 0.000706

Gnomad4 OTH AF: 0.00894

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3831942; hg19: chr1-154842199;