11-74456155-AATATAT-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005472.5(KCNE3):c.*1091_*1096del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.60 (19182 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: KCNE3 NM_005472.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.296

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNE3	NM_005472.5	c.*1091_*1096del		3_prime_UTR_variant	3/3	ENST00000310128.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNE3	ENST00000310128.9	c.*1091_*1096del		3_prime_UTR_variant	3/3	1	NM_005472.5	P1
	ENST00000530510.1	n.425+403_425+408del		intron_variant, non_coding_transcript_variant		2
	ENST00000533008.1	n.155-28002_155-27997del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.599 AC: 67758 AN: 113038 Hom.: 19178 Cov.: 0

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.599 AC: 67767 AN: 113062 Hom.: 19182 Cov.: 0 AF XY: 0.612 AC XY: 32648 AN XY: 53316

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.616

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Brugada syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs113583236; hg19: chr11-74167200;