Genetic Variant KCNJ5:c.-296_-295insGAGA (chr11-128891435-C-CAGAG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000890.5(KCNJ5):c.-296_-295insGAGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00348 in 84,650 control chromosomes in the GnomAD database, including 2 homozygotes. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 26)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNJ5
NM_000890.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.342

Publications

0 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 links:

KCNJ5-AS1 (HGNC:28584): (KCNJ5 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

KCNJ5-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ5	NM_000890.5 link	c.-296_-295insGAGA		5_prime_UTR_variant	Exon 1 of 3	ENST00000529694.6	NP_000881.3	P48544A0A5J6E2W8
KCNJ5	NM_001354169.2 link	c.-385_-384insGAGA		5_prime_UTR_variant	Exon 1 of 4		NP_001341098.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNJ5	ENST00000529694.6 link	c.-296_-295insGAGA	5_prime_UTR_variant	Exon 1 of 3	1	NM_000890.5	ENSP00000433295.1	P48544
KCNJ5-AS1	ENST00000730925.1 link	n.314+12995_314+12996insCTCT	intron_variant	Intron 2 of 2
KCNJ5-AS1	ENST00000730926.1 link	n.285+12995_285+12996insCTCT	intron_variant	Intron 2 of 2
KCNJ5	ENST00000338350.4 link	c.-386_-385insAGAG	upstream_gene_variant		1		ENSP00000339960.4	P48544

Frequencies

GnomAD3 genomes

AF:

0.00349

AC:

295

AN:

84598

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00628

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00270

Gnomad ASJ

AF:

0.00327

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000505

Gnomad FIN

AF:

0.00180

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00296

Gnomad OTH

AF:

0.00377

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

412

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

318

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

378

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.00348

AC:

295

AN:

84650

Hom.:

Cov.:

AF XY:

0.00373

AC XY:

149

AN XY:

39992

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00626

AC:

121

AN:

19324

American (AMR)

AF:

0.00269

AC:

AN:

8922

Ashkenazi Jewish (ASJ)

AF:

0.00327

AC:

AN:

2138

East Asian (EAS)

AF:

0.00

AC:

AN:

2402

South Asian (SAS)

AF:

0.000508

AC:

AN:

1968

European-Finnish (FIN)

AF:

0.00180

AC:

AN:

4990

Middle Eastern (MID)

AF:

0.00

AC:

AN:

150

European-Non Finnish (NFE)

AF:

0.00296

AC:

128

AN:

43228

Other (OTH)

AF:

0.00373

AC:

AN:

1072

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.364

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.34

Mutation Taster

=298/2

polymorphism

(source)

Splicing

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

Publications

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11-128891435-C-CAGAG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over