Genetic Variant KCNE3:c.*921_*922dupTT (chr11-74456329-C-CAA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_005472.5(KCNE3):c.*921_*922dupTT 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 0.0072 ( 14 hom., cov: 0)

Exomes 𝑓: 0.034 ( 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: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00724 (874/120640) while in subpopulation AFR AF = 0.0256 (805/31418). AF 95% confidence interval is 0.0242. There are 14 homozygotes in GnomAd4. There are 415 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 874 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.921_922dupTT		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.921_922dupTT	3_prime_UTR	Exon 3 of 3	ENSP00000310557.4	Q9Y6H6
KCNE3	ENST00000875764.1		c.921_922dupTT	3_prime_UTR	Exon 4 of 4	ENSP00000545823.1
KCNE3	ENST00000929452.1		c.921_922dupTT	3_prime_UTR	Exon 4 of 4	ENSP00000599511.1

Frequencies

GnomAD3 genomes

AF:

0.00726

AC:

876

AN:

120654

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00354

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000822

Gnomad FIN

AF:

0.000368

Gnomad MID

AF:

0.00781

Gnomad NFE

AF:

0.000240

Gnomad OTH

AF:

0.00427

GnomAD4 exome

AF:

0.0345

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0238

AC XY:

AN XY:

show subpopulations

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:

0.0400

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00724

AC:

874

AN:

120640

Hom.:

Cov.:

AF XY:

0.00727

AC XY:

415

AN XY:

57084

show subpopulations

African (AFR)

AF:

0.0256

AC:

805

AN:

31418

American (AMR)

AF:

0.00353

AC:

AN:

11882

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3112

East Asian (EAS)

AF:

0.00

AC:

AN:

4156

South Asian (SAS)

AF:

0.000828

AC:

AN:

3624

European-Finnish (FIN)

AF:

0.000368

AC:

AN:

5442

Middle Eastern (MID)

AF:

0.00833

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.000223

AC:

AN:

58306

Other (OTH)

AF:

0.00425

AC:

AN:

1646

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

101

135

169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

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

Publications

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11-74456329-CAAAAA-CAAAAAAA

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