11-74456155-AATATATATATATAT-AATATATAT

Variant names:

• chr11-74456155-AATATAT-A
• rs113583236
• NM_005472.5:c.*1091_*1096delATATAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_005472.5(KCNE3):​c.*1091_*1096delATATAT 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, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.296
• Publications: 0 publications found

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

ENSG00000254928 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

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.*1091_*1096delATATAT		3_prime_UTR	Exon 3 of 3	NP_005463.1	Q9Y6H6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE3	ENST00000310128.9	TSL:1 MANE Select	c.*1091_*1096delATATAT		3_prime_UTR	Exon 3 of 3	ENSP00000310557.4	Q9Y6H6
	KCNE3	ENST00000875764.1		c.*1091_*1096delATATAT		3_prime_UTR	Exon 4 of 4	ENSP00000545823.1
	KCNE3	ENST00000929452.1		c.*1091_*1096delATATAT		3_prime_UTR	Exon 4 of 4	ENSP00000599511.1

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

African (AFR) AF: 0.667 AC: 22940 AN: 34400

American (AMR) AF: 0.657 AC: 6831 AN: 10400

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 1718 AN: 2828

East Asian (EAS) AF: 0.479 AC: 1543 AN: 3222

South Asian (SAS) AF: 0.696 AC: 2278 AN: 3274

European-Finnish (FIN) AF: 0.704 AC: 2929 AN: 4158

Middle Eastern (MID) AF: 0.657 AC: 138 AN: 210

European-Non Finnish (NFE) AF: 0.533 AC: 27897 AN: 52292

Other (OTH) AF: 0.616 AC: 921 AN: 1496

Alfa AF: 0.476 Hom.: 640

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Brugada syndrome (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs113583236; hg19: chr11-74167200;