Genetic Variant KCNE3:c.*922dupT (chr11-74456329-C-CA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005472.5(KCNE3):c.*922dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 0)

Exomes 𝑓: 0.069 ( 0 hom. )

Consequence

KCNE3
NM_005472.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.554

Publications

1 publications found

Variant links:

Genes affected

KCNE3 (HGNC:6243): (potassium voltage-gated channel subfamily E regulatory subunit 3) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, isk-related subfamily. This member is a type I membrane protein, and a beta subunit that assembles with a potassium channel alpha-subunit to modulate the gating kinetics and enhance stability of the multimeric complex. This gene is prominently expressed in the kidney. A missense mutation in this gene is associated with hypokalemic periodic paralysis. [provided by RefSeq, Jul 2008]

KCNE3 Gene-Disease associations (from GenCC):

Brugada syndrome 6
Inheritance: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
Brugada syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

KCNE3 links:

ENSG00000254928 (HGNC:):

ENSG00000254928 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 50 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005472.5. 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
	KCNE3	NM_005472.5	MANE Select	c.*922dupT		3_prime_UTR	Exon 3 of 3	NP_005463.1	Q9Y6H6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNE3	ENST00000310128.9	TSL:1 MANE Select	c.*922dupT	3_prime_UTR	Exon 3 of 3	ENSP00000310557.4	Q9Y6H6
KCNE3	ENST00000875764.1		c.*922dupT	3_prime_UTR	Exon 4 of 4	ENSP00000545823.1
KCNE3	ENST00000929452.1		c.*922dupT	3_prime_UTR	Exon 4 of 4	ENSP00000599511.1

Frequencies

GnomAD3 genomes

AF:

0.000423

AC:

AN:

120634

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000319

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000253

Gnomad ASJ

AF:

0.000321

Gnomad EAS

AF:

0.00144

Gnomad SAS

AF:

0.000274

Gnomad FIN

AF:

0.000551

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000446

Gnomad OTH

AF:

0.000610

GnomAD4 exome

AF:

0.0690

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0476

AC XY:

AN XY:

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0800

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00180467), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000415

AC:

AN:

120620

Hom.:

Cov.:

AF XY:

0.000473

AC XY:

AN XY:

57072

show subpopulations

African (AFR)

AF:

0.000318

AC:

AN:

31414

American (AMR)

AF:

0.000253

AC:

AN:

11880

Ashkenazi Jewish (ASJ)

AF:

0.000321

AC:

AN:

3112

East Asian (EAS)

AF:

0.00144

AC:

AN:

4156

South Asian (SAS)

AF:

0.00

AC:

AN:

3624

European-Finnish (FIN)

AF:

0.000551

AC:

AN:

5440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.000446

AC:

AN:

58294

Other (OTH)

AF:

0.000608

AC:

AN:

1646

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.55

Mutation Taster

=100/0

polymorphism

(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

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

11-74456329-CAAAAA-CAAAAAA

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