11-74455736-G-GT

Variant summary

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

The NM_005472.5(KCNE3):c.*1515_*1516insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (6156 hom., cov: 0)
  • Exomes 𝑓: 0.053 (0 hom.)
• Consequence: KCNE3 NM_005472.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.519

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 -10 ACMG points.

• BP6: Variant 11-74455736-G-GT is Benign according to our data. Variant chr11-74455736-G-GT is described in ClinVar as [Likely_benign]. Clinvar id is 306040.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNE3	NM_005472.5	c.*1515_*1516insA		3_prime_UTR_variant	3/3	ENST00000310128.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNE3	ENST00000310128.9	c.*1515_*1516insA		3_prime_UTR_variant	3/3	1	NM_005472.5	P1
	ENST00000530510.1	n.398dup		non_coding_transcript_exon_variant	1/2	2
	ENST00000533008.1	n.155-28432dup		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.239 AC: 35491 AN: 148660 Hom.: 6145 Cov.: 0

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.198

GnomAD4 exome AF: 0.0526 AC: 2 AN: 38 Hom.: 0 Cov.: 0 AF XY: 0.0625 AC XY: 2 AN XY: 32

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0333

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.239 AC: 35534 AN: 148766 Hom.: 6156 Cov.: 0 AF XY: 0.242 AC XY: 17541 AN XY: 72476

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.197

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: rs41315535; hg19: chr11-74166781;