Genetic Variant KCNE3:c.*1096_*1097insATATATATATATATATATATATATATAT (chr11-74456155-A-AATATATATATATATATATATATATATAT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_005472.5(KCNE3):c.*1096_*1097insATATATATATATATATATATATATATAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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 0.00083 ( 1 hom., cov: 0)

Consequence

KCNE3
NM_005472.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.296

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

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.1096_1097insATATATATATATATATATATATATATAT		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.1096_1097insATATATATATATATATATATATATATAT	3_prime_UTR	Exon 3 of 3	ENSP00000310557.4	Q9Y6H6
KCNE3	ENST00000875764.1		c.1096_1097insATATATATATATATATATATATATATAT	3_prime_UTR	Exon 4 of 4	ENSP00000545823.1
KCNE3	ENST00000929452.1		c.1096_1097insATATATATATATATATATATATATATAT	3_prime_UTR	Exon 4 of 4	ENSP00000599511.1

Frequencies

GnomAD3 genomes

AF:

0.000840

AC:

AN:

113060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000233

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000771

Gnomad ASJ

AF:

0.00601

Gnomad EAS

AF:

0.00186

Gnomad SAS

AF:

0.00212

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000918

Gnomad OTH

AF:

0.000674

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.000831

AC:

AN:

113084

Hom.:

Cov.:

AF XY:

0.000656

AC XY:

AN XY:

53328

show subpopulations

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

African (AFR)

AF:

0.000232

AC:

AN:

34432

American (AMR)

AF:

0.000770

AC:

AN:

10392

Ashkenazi Jewish (ASJ)

AF:

0.00601

AC:

AN:

2830

East Asian (EAS)

AF:

0.00186

AC:

AN:

3220

South Asian (SAS)

AF:

0.00214

AC:

AN:

3278

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4156

Middle Eastern (MID)

AF:

0.00

AC:

AN:

208

European-Non Finnish (NFE)

AF:

0.000899

AC:

AN:

52288

Other (OTH)

AF:

0.000668

AC:

AN:

1498

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.356

Heterozygous variant carriers

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.30

Splicing

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

Publications

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11-74456155-AATATATATATATAT-AATATATATATATATATATATATATATATATATATATATATAT

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