11-74456341-AAG-A

Position:

• chr11-74456341-AAG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005472.5(KCNE3):​c.*909_*910delCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 129,112 control chromosomes in the GnomAD database, including 2,741 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (2741 hom., cov: 23)
  • Exomes 𝑓: 0.0072 (0 hom.)
• Consequence: KCNE3 NM_005472.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.341

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]

ENSG00000254928 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-74456341-AAG-A is Benign according to our data. Variant chr11-74456341-AAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 306064.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNE3	NM_005472.5	c.*909_*910delCT		3_prime_UTR_variant	3/3	ENST00000310128.9	NP_005463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNE3	ENST00000310128	c.*909_*910delCT		3_prime_UTR_variant	3/3	1	NM_005472.5	ENSP00000310557.4
ENSG00000254928	ENST00000530510.1	n.426-299_426-298delGA		intron_variant		2
ENSG00000254631	ENST00000533008.1	n.155-27834_155-27833delGA		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.202 AC: 25997 AN: 128954 Hom.: 2736 Cov.: 23

Gnomad AFR AF: 0.0744

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.200

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.00725 AC: 1 AN: 138 Hom.: 0 AF XY: 0.00943 AC XY: 1 AN XY: 106

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.202 AC: 26004 AN: 128974 Hom.: 2741 Cov.: 23 AF XY: 0.201 AC XY: 12549 AN XY: 62574

Gnomad4 AFR AF: 0.0742

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.230

Alfa AF: 0.180 Hom.: 9

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Brugada syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs757362085; hg19: chr11-74167386;