NM_002240.5:c.*9564C>T

Variant names:

• chr21-37615595-G-A
• rs2835833
• NM_002240.5:c.*9564C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002240.5(KCNJ6):​c.*9564C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,998 control chromosomes in the GnomAD database, including 7,601 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 0.31 (7601 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNJ6 NM_002240.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• 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]

ENSG00000286717 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	NM_002240.5	MANE Select	c.*9564C>T		3_prime_UTR	Exon 4 of 4	NP_002231.1	P48051
	KCNJ6-AS1	NR_183540.1		n.408-82960G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	ENST00000609713.2	TSL:1 MANE Select	c.*9564C>T		3_prime_UTR	Exon 4 of 4	ENSP00000477437.1	P48051
	ENSG00000286717	ENST00000667151.1		n.160+21459G>A		intron	N/A
	ENSG00000286717	ENST00000838658.1		n.234+21459G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47316 AN: 151880 Hom.: 7584 Cov.: 31

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.309

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.312 AC: 47376 AN: 151998 Hom.: 7601 Cov.: 31 AF XY: 0.313 AC XY: 23225 AN XY: 74310

African (AFR) AF: 0.313 AC: 12973 AN: 41440

American (AMR) AF: 0.250 AC: 3815 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1128 AN: 3464

East Asian (EAS) AF: 0.208 AC: 1079 AN: 5182

South Asian (SAS) AF: 0.347 AC: 1670 AN: 4814

European-Finnish (FIN) AF: 0.365 AC: 3853 AN: 10552

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21606 AN: 67962

Other (OTH) AF: 0.310 AC: 652 AN: 2104

Alfa AF: 0.314 Hom.: 20829

Bravo AF: 0.305

Asia WGS AF: 0.254 AC: 886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.8
DANN	Benign	0.75
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs2835833; hg19: chr21-38987897;