11-74456155-AATATATATATATAT-AATATATATATATATATATATATAT

Variant names:

• chr11-74456155-A-AATATATATAT
• rs113583236
• NM_005472.5:c.*1087_*1096dupATATATATAT

Variant summary

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

The NM_005472.5(KCNE3):​c.*1087_*1096dupATATATATAT 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 0.083 (688 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 (EAS) allele frequency at 95% confidence interval = 0.128 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.*1087_*1096dupATATATATAT		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.*1087_*1096dupATATATATAT		3_prime_UTR	Exon 3 of 3	ENSP00000310557.4	Q9Y6H6
	KCNE3	ENST00000875764.1		c.*1087_*1096dupATATATATAT		3_prime_UTR	Exon 4 of 4	ENSP00000545823.1
	KCNE3	ENST00000929452.1		c.*1087_*1096dupATATATATAT		3_prime_UTR	Exon 4 of 4	ENSP00000599511.1

Frequencies

GnomAD3 genomes AF: 0.0830 AC: 9349 AN: 112648 Hom.: 686 Cov.: 0

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0609

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.0380

Gnomad FIN AF: 0.0745

Gnomad MID AF: 0.0315

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0758

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0830 AC: 9353 AN: 112668 Hom.: 688 Cov.: 0 AF XY: 0.0793 AC XY: 4211 AN XY: 53102

African (AFR) AF: 0.0232 AC: 798 AN: 34382

American (AMR) AF: 0.121 AC: 1246 AN: 10310

Ashkenazi Jewish (ASJ) AF: 0.0609 AC: 172 AN: 2826

East Asian (EAS) AF: 0.138 AC: 442 AN: 3194

South Asian (SAS) AF: 0.0379 AC: 124 AN: 3268

European-Finnish (FIN) AF: 0.0745 AC: 306 AN: 4106

Middle Eastern (MID) AF: 0.0337 AC: 7 AN: 208

European-Non Finnish (NFE) AF: 0.117 AC: 6098 AN: 52112

Other (OTH) AF: 0.0744 AC: 111 AN: 1492

Alfa AF: 0.160 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;