Genetic Variant KCNE3:c.*1093_*1096delATAT (chr11-74456155-AATAT-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_005472.5(KCNE3):c.*1093_*1096delATAT 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 0.017 ( 42 hom., cov: 0)

Failed GnomAD Quality Control

Consequence

KCNE3
NM_005472.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.296

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 links:

ENSG00000254928 (HGNC:):

ENSG00000254928 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0174 (1971/113062) while in subpopulation AFR AF= 0.0209 (721/34418). AF 95% confidence interval is 0.0197. There are 42 homozygotes in gnomad4. There are 927 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1971 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNE3	NM_005472.5 link	c.1093_1096delATAT		3_prime_UTR_variant	Exon 3 of 3	ENST00000310128.9	NP_005463.1	Q9Y6H6Q6IAE6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNE3	ENST00000310128 link	c.1093_1096delATAT	3_prime_UTR_variant	Exon 3 of 3	1	NM_005472.5	ENSP00000310557.4	Q9Y6H6
ENSG00000254928	ENST00000530510.1 link	n.425+405_425+408delTATA	intron_variant	Intron 1 of 1	2
ENSG00000254631	ENST00000533008.1 link	n.155-28000_155-27997delTATA	intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.0175

AC:

1973

AN:

113038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0210

Gnomad AMI

AF:

0.00384

Gnomad AMR

AF:

0.00935

Gnomad ASJ

AF:

0.00813

Gnomad EAS

AF:

0.000926

Gnomad SAS

AF:

0.0100

Gnomad FIN

AF:

0.0164

Gnomad MID

AF:

0.00901

Gnomad NFE

AF:

0.0190

Gnomad OTH

AF:

0.0169

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0174

AC:

1971

AN:

113062

Hom.:

Cov.:

AF XY:

0.0174

AC XY:

927

AN XY:

53300

show subpopulations

Gnomad4 AFR

AF:

0.0209

Gnomad4 AMR

AF:

0.00934

Gnomad4 ASJ

AF:

0.00813

Gnomad4 EAS

AF:

0.000930

Gnomad4 SAS

AF:

0.0101

Gnomad4 FIN

AF:

0.0164

Gnomad4 NFE

AF:

0.0190

Gnomad4 OTH

AF:

0.0167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing