chr21-38299548-A-G

Variant names:

• chr21-38299548-A-G
• rs1985536878
• NM_170736.3:c.287A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_170736.3(KCNJ15):​c.287A>G​(p.Glu96Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KCNJ15 NM_170736.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.96
• Publications: 0 publications found

Genes affected

KCNJ15 (HGNC:6261): (potassium inwardly rectifying channel subfamily J member 15) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Eight transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35775787).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170736.3. 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
	KCNJ15	NM_170736.3	MANE Select	c.287A>G	p.Glu96Gly	missense	Exon 3 of 3	NP_733932.1	Q99712
	KCNJ15	NM_001276435.2		c.287A>G	p.Glu96Gly	missense	Exon 5 of 5	NP_001263364.1	Q99712
	KCNJ15	NM_001276436.2		c.287A>G	p.Glu96Gly	missense	Exon 5 of 5	NP_001263365.1	Q99712

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ15	ENST00000398938.7	TSL:1 MANE Select	c.287A>G	p.Glu96Gly	missense	Exon 3 of 3	ENSP00000381911.2	Q99712
	KCNJ15	ENST00000328656.8	TSL:1	c.287A>G	p.Glu96Gly	missense	Exon 4 of 4	ENSP00000331698.3	Q99712
	KCNJ15	ENST00000398930.5	TSL:5	c.287A>G	p.Glu96Gly	missense	Exon 4 of 4	ENSP00000381904.1	Q99712

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74306

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.0000655 AC: 1 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Uncertain	0.60	D
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.36	T
MetaSVM	Uncertain	0.10	D
MutationAssessor	Benign	2.0	M
PhyloP100		3.0
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.40
Sift	Benign	0.11	T
Sift4G	Benign	0.35	T
Polyphen		0.58	P
Vest4		0.17
MutPred		0.47		Loss of solvent accessibility (P = 0.0477)
MVP		0.78
MPC		0.67
ClinPred		0.37	T
GERP RS		5.1
Varity_R		0.14
gMVP		0.91
Mutation Taster		=83/17	polymorphism

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: rs1985536878; hg19: chr21-39671470;