21-37632245-A-AGGCCGGGCCGGAAGCGCGTTGGCCACGCCTGTCAGCCCCGCACTTTGGAGCCGTTAGGCGGGTGTATCATGAGGTCCGAGATCGCAGACACCATATCCTGTCTCACAACAAGGTGACCCCCCTCCTCTACTAAAAACTCCACACATTAGCCGGGCGCAGTGGCGGGCGCCTGTAGTTCCCAGCTACTCCGGGCAGGCTAGAGGACAGGAGAAATAGAGTGCGTGCACCCCGGCCAGCGGAGCTTGCAGCTGGCGCACTAGATTGCGCCACTGCAGTCCGCCGTCGCGGCCTAGGGCCGACAGAGCGAGAACTCCGTCTCCAACAACAAAAAACACACACCACAAACAAAC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002240.5(KCNJ6):c.947-6762_947-6761insGTTTGTTTGTGGTGTGTGTTTTTTGTTGTTGGAGACGGAGTTCTCGCTCTGTCGGCCCTAGGCCGCGACGGCGGACTGCAGTGGCGCAATCTAGTGCGCCAGCTGCAAGCTCCGCTGGCCGGGGTGCACGCACTCTATTTCTCCTGTCCTCTAGCCTGCCCGGAGTAGCTGGGAACTACAGGCGCCCGCCACTGCGCCCGGCTAATGTGTGGAGTTTTTAGTAGAGGAGGGGGGTCACCTTGTTGTGAGACAGGATATGGTGTCTGCGATCTCGGACCTCATGATACACCCGCCTAACGGCTCCAAAGTGCGGGGCTGACAGGCGTGGCCAACGCGCTTCCGGCCCGGCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.114

Genes affected

KCNJ6 (HGNC:6267): (potassium inwardly rectifying channel subfamily J member 6) This gene encodes a member of the G protein-coupled inwardly-rectifying potassium channel family of inward rectifier potassium channels. This type of potassium channel allows a greater flow of potassium into the cell than out of it. These proteins modulate many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells, through G-protein coupled receptor stimulation. Mutations in this gene are associated with Keppen-Lubinsky Syndrome, a rare condition characterized by severe developmental delay, facial dysmorphism, and intellectual disability. [provided by RefSeq, Apr 2015]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ6	NM_002240.5	c.947-6762_947-6761insGTTTGTTTGTGGTGTGTGTTTTTTGTTGTTGGAGACGGAGTTCTCGCTCTGTCGGCCCTAGGCCGCGACGGCGGACTGCAGTGGCGCAATCTAGTGCGCCAGCTGCAAGCTCCGCTGGCCGGGGTGCACGCACTCTATTTCTCCTGTCCTCTAGCCTGCCCGGAGTAGCTGGGAACTACAGGCGCCCGCCACTGCGCCCGGCTAATGTGTGGAGTTTTTAGTAGAGGAGGGGGGTCACCTTGTTGTGAGACAGGATATGGTGTCTGCGATCTCGGACCTCATGATACACCCGCCTAACGGCTCCAAAGTGCGGGGCTGACAGGCGTGGCCAACGCGCTTCCGGCCCGGCC		intron_variant		ENST00000609713.2
KCNJ6-AS1	NR_183540.1	n.408-66310_408-66309insGGCCGGGCCGGAAGCGCGTTGGCCACGCCTGTCAGCCCCGCACTTTGGAGCCGTTAGGCGGGTGTATCATGAGGTCCGAGATCGCAGACACCATATCCTGTCTCACAACAAGGTGACCCCCCTCCTCTACTAAAAACTCCACACATTAGCCGGGCGCAGTGGCGGGCGCCTGTAGTTCCCAGCTACTCCGGGCAGGCTAGAGGACAGGAGAAATAGAGTGCGTGCACCCCGGCCAGCGGAGCTTGCAGCTGGCGCACTAGATTGCGCCACTGCAGTCCGCCGTCGCGGCCTAGGGCCGACAGAGCGAGAACTCCGTCTCCAACAACAAAAAACACACACCACAAACAAAC		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ6	ENST00000609713.2	c.947-6762_947-6761insGTTTGTTTGTGGTGTGTGTTTTTTGTTGTTGGAGACGGAGTTCTCGCTCTGTCGGCCCTAGGCCGCGACGGCGGACTGCAGTGGCGCAATCTAGTGCGCCAGCTGCAAGCTCCGCTGGCCGGGGTGCACGCACTCTATTTCTCCTGTCCTCTAGCCTGCCCGGAGTAGCTGGGAACTACAGGCGCCCGCCACTGCGCCCGGCTAATGTGTGGAGTTTTTAGTAGAGGAGGGGGGTCACCTTGTTGTGAGACAGGATATGGTGTCTGCGATCTCGGACCTCATGATACACCCGCCTAACGGCTCCAAAGTGCGGGGCTGACAGGCGTGGCCAACGCGCTTCCGGCCCGGCC		intron_variant		1	NM_002240.5	P1
	ENST00000667151.1	n.161-14302_161-14301insGGCCGGGCCGGAAGCGCGTTGGCCACGCCTGTCAGCCCCGCACTTTGGAGCCGTTAGGCGGGTGTATCATGAGGTCCGAGATCGCAGACACCATATCCTGTCTCACAACAAGGTGACCCCCCTCCTCTACTAAAAACTCCACACATTAGCCGGGCGCAGTGGCGGGCGCCTGTAGTTCCCAGCTACTCCGGGCAGGCTAGAGGACAGGAGAAATAGAGTGCGTGCACCCCGGCCAGCGGAGCTTGCAGCTGGCGCACTAGATTGCGCCACTGCAGTCCGCCGTCGCGGCCTAGGGCCGACAGAGCGAGAACTCCGTCTCCAACAACAAAAAACACACACCACAAACAAAC		intron_variant, non_coding_transcript_variant
KCNJ6	ENST00000645093.1	c.947-6762_947-6761insGTTTGTTTGTGGTGTGTGTTTTTTGTTGTTGGAGACGGAGTTCTCGCTCTGTCGGCCCTAGGCCGCGACGGCGGACTGCAGTGGCGCAATCTAGTGCGCCAGCTGCAAGCTCCGCTGGCCGGGGTGCACGCACTCTATTTCTCCTGTCCTCTAGCCTGCCCGGAGTAGCTGGGAACTACAGGCGCCCGCCACTGCGCCCGGCTAATGTGTGGAGTTTTTAGTAGAGGAGGGGGGTCACCTTGTTGTGAGACAGGATATGGTGTCTGCGATCTCGGACCTCATGATACACCCGCCTAACGGCTCCAAAGTGCGGGGCTGACAGGCGTGGCCAACGCGCTTCCGGCCCGGCC		intron_variant				P1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Schizophrenia Uncertain:1

Uncertain significance, no assertion criteria provided

case-control

Department of Psychiatry, The University of Hong Kong

Nov 11, 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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-39004547;