11-128911444-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000890.5(KCNJ5):c.171T>C(p.Ser57Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 1,614,136 control chromosomes in the GnomAD database, including 554,035 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55013 hom., cov: 33)

Exomes 𝑓: 0.83 ( 499022 hom. )

Consequence

KCNJ5
NM_000890.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -2.31

Publications

39 publications found

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 Gene-Disease associations (from GenCC):

familial hyperaldosteronism type III
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
Andersen-Tawil syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
long QT syndrome 13
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
long QT syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

KCNJ5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 11-128911444-T-C is Benign according to our data. Variant chr11-128911444-T-C is described in ClinVar as Benign. ClinVar VariationId is 137990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000890.5. 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
	KCNJ5	NM_000890.5	MANE Select	c.171T>C	p.Ser57Ser	synonymous	Exon 2 of 3	NP_000881.3
	KCNJ5	NM_001354169.2		c.171T>C	p.Ser57Ser	synonymous	Exon 3 of 4	NP_001341098.1	P48544

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNJ5	ENST00000529694.6	TSL:1 MANE Select	c.171T>C	p.Ser57Ser	synonymous	Exon 2 of 3	ENSP00000433295.1	P48544
KCNJ5	ENST00000338350.4	TSL:1	c.171T>C	p.Ser57Ser	synonymous	Exon 3 of 4	ENSP00000339960.4	P48544
KCNJ5	ENST00000533599.1	TSL:1	c.171T>C	p.Ser57Ser	synonymous	Exon 1 of 2	ENSP00000434266.1	P48544

Frequencies

GnomAD3 genomes

AF:

0.849

AC:

129135

AN:

152136

Hom.:

54968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.903

Gnomad AMI

AF:

0.865

Gnomad AMR

AF:

0.838

Gnomad ASJ

AF:

0.841

Gnomad EAS

AF:

0.879

Gnomad SAS

AF:

0.893

Gnomad FIN

AF:

0.797

Gnomad MID

AF:

0.826

Gnomad NFE

AF:

0.821

Gnomad OTH

AF:

0.861

GnomAD2 exomes

AF:

0.840

AC:

211299

AN:

251440

AF XY:

0.844

show subpopulations

Gnomad AFR exome

AF:

0.905

Gnomad AMR exome

AF:

0.814

Gnomad ASJ exome

AF:

0.848

Gnomad EAS exome

AF:

0.880

Gnomad FIN exome

AF:

0.793

Gnomad NFE exome

AF:

0.827

Gnomad OTH exome

AF:

0.838

GnomAD4 exome

AF:

0.826

AC:

1207009

AN:

1461880

Hom.:

499022

Cov.:

AF XY:

0.829

AC XY:

602766

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.909

AC:

30447

AN:

33480

American (AMR)

AF:

0.814

AC:

36383

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.847

AC:

22150

AN:

26136

East Asian (EAS)

AF:

0.872

AC:

34634

AN:

39700

South Asian (SAS)

AF:

0.890

AC:

76801

AN:

86258

European-Finnish (FIN)

AF:

0.790

AC:

42189

AN:

53420

Middle Eastern (MID)

AF:

0.886

AC:

5109

AN:

5768

European-Non Finnish (NFE)

AF:

0.817

AC:

908996

AN:

1111998

Other (OTH)

AF:

0.833

AC:

50300

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

14050

28100

42149

56199

70249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20946

41892

62838

83784

104730

<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:

0.849

AC:

129236

AN:

152256

Hom.:

55013

Cov.:

AF XY:

0.849

AC XY:

63213

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.903

AC:

37517

AN:

41560

American (AMR)

AF:

0.838

AC:

12823

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.841

AC:

2921

AN:

3472

East Asian (EAS)

AF:

0.880

AC:

4545

AN:

5166

South Asian (SAS)

AF:

0.893

AC:

4305

AN:

4822

European-Finnish (FIN)

AF:

0.797

AC:

8453

AN:

10604

Middle Eastern (MID)

AF:

0.823

AC:

242

AN:

294

European-Non Finnish (NFE)

AF:

0.821

AC:

55824

AN:

68010

Other (OTH)

AF:

0.860

AC:

1817

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1047

2094

3140

4187

5234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.838

Hom.:

62959

Bravo

AF:

0.853

Asia WGS

AF:

0.883

AC:

3068

AN:

3478

EpiCase

AF:

0.836

EpiControl

AF:

0.835

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

Familial hyperaldosteronism type III (2)

Cardiovascular phenotype (1)

Congenital long QT syndrome (1)

Long QT syndrome (1)

Long QT syndrome 13 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.63

(source)

DANN

Benign

0.60

PhyloP100

-2.3

PromoterAI

0.0084

Neutral

(source)

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over