Genetic Variant KCNJ15:p.Ala3Val (chr21-38299269-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_170736.3(KCNJ15):c.8C>T(p.Ala3Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,610,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

KCNJ15
NM_170736.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

Publications

0 publications found

Variant links:

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]

KCNJ15 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.11188173).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNJ15	NM_170736.3	MANE Select	c.8C>T	p.Ala3Val	missense	Exon 3 of 3	NP_733932.1	Q99712
KCNJ15	NM_001276435.2		c.8C>T	p.Ala3Val	missense	Exon 5 of 5	NP_001263364.1	Q99712
KCNJ15	NM_001276436.2		c.8C>T	p.Ala3Val	missense	Exon 5 of 5	NP_001263365.1	Q99712

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNJ15	ENST00000398938.7	TSL:1 MANE Select	c.8C>T	p.Ala3Val	missense	Exon 3 of 3	ENSP00000381911.2	Q99712
KCNJ15	ENST00000328656.8	TSL:1	c.8C>T	p.Ala3Val	missense	Exon 4 of 4	ENSP00000331698.3	Q99712
KCNJ15	ENST00000398930.5	TSL:5	c.8C>T	p.Ala3Val	missense	Exon 4 of 4	ENSP00000381904.1	Q99712

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458030

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724820

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33396

American (AMR)

AF:

0.00

AC:

AN:

44474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25864

East Asian (EAS)

AF:

0.00

AC:

AN:

39602

South Asian (SAS)

AF:

0.00

AC:

AN:

86000

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53338

Middle Eastern (MID)

AF:

0.000523

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1109382

Other (OTH)

AF:

0.00

AC:

AN:

60242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

9.6

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.096

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.60

M_CAP

Benign

0.057

MetaRNN

Benign

0.11

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

1.5

PhyloP100

3.5

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.28

Sift

Uncertain

0.017

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.050

MutPred

0.30

Gain of sheet (P = 0.0149)

MVP

0.74

MPC

0.46

ClinPred

0.33

GERP RS

3.1

Varity_R

0.070

gMVP

0.74

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over