rs1399592

Variant names:

• chr21-37681559-T-A
• rs1399592
• NM_002240.5:c.946+32652A>T

Your query was ambiguous. Multiple possible variants found:

• chr21-37681559-T-A
• chr21-37681559-T-C
• chr21-37681559-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002240.5(KCNJ6):​c.946+32652A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643
• Publications: 3 publications found

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]

KCNJ6-AS1 (HGNC:):

KCNJ6-AS1 (HGNC:41352): (KCNJ6 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002240.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	NM_002240.5	MANE Select	c.946+32652A>T		intron	N/A	NP_002231.1
	KCNJ6-AS1	NR_183540.1		n.408-16996T>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	ENST00000609713.2	TSL:1 MANE Select	c.946+32652A>T		intron	N/A	ENSP00000477437.1
	KCNJ6	ENST00000645093.1		c.946+32652A>T		intron	N/A	ENSP00000493772.1
	KCNJ6-AS1	ENST00000838485.1		n.87-28755T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.1
DANN	Benign	0.87
PhyloP100		-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

Other links and lift over

dbSNP: rs1399592; hg19: chr21-39053862;