rs771919907

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_000890.5(KCNJ5):c.864G>T(p.Glu288Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,460,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

KCNJ5
NM_000890.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 4.75

Variant links:

Genes affected

KCNJ5 (HGNC:6266): (potassium inwardly rectifying channel subfamily J member 5) This gene encodes an integral membrane protein which belongs to one of seven subfamilies of inward-rectifier potassium channel proteins called potassium channel subfamily J. The encoded protein is a subunit of the potassium channel which is homotetrameric. It is controlled by G-proteins and has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Naturally occurring mutations in this gene are associated with aldosterone-producing adenomas. [provided by RefSeq, Aug 2017]

KCNJ5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21763122).

BP6

Variant 11-128912137-G-T is Benign according to our data. Variant chr11-128912137-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 560690.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High AC in GnomAdExome at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KCNJ5	NM_000890.5 linkuse as main transcript	c.864G>T	p.Glu288Asp	missense_variant	2/3	ENST00000529694.6
KCNJ5	NM_001354169.2 linkuse as main transcript	c.864G>T	p.Glu288Asp	missense_variant	3/4
KCNJ5	XM_011542810.4 linkuse as main transcript	c.864G>T	p.Glu288Asp	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
KCNJ5	ENST00000529694.6 linkuse as main transcript	c.864G>T	p.Glu288Asp	missense_variant	2/3	1	NM_000890.5	P1
KCNJ5	ENST00000338350.4 linkuse as main transcript	c.864G>T	p.Glu288Asp	missense_variant	3/4	1		P1
KCNJ5	ENST00000533599.1 linkuse as main transcript	c.864G>T	p.Glu288Asp	missense_variant	1/2	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000244

AC:

AN:

245480

Hom.:

AF XY:

0.0000225

AC XY:

AN XY:

133070

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1460118

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726348

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Long QT syndrome 13

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues

Dec 20, 2017

- -

Hypertrophic cardiomyopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego

Feb 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.16

Cadd

Benign

Dann

Benign

0.86

DEOGEN2

Uncertain

0.53

D;D;D

Eigen

Benign

-0.21

Eigen_PC

Benign

0.047

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.034

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.14

N;N;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.25

N;N;N

REVEL

Benign

0.26

Sift

Benign

0.53

T;T;T

Sift4G

Benign

0.57

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.27

MutPred

0.48

Loss of disorder (P = 0.1447);Loss of disorder (P = 0.1447);Loss of disorder (P = 0.1447);

MVP

0.83

MPC

0.39

ClinPred

0.066

GERP RS

5.5

Varity_R

0.22

gMVP

0.53

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over