NM_005472.5:c.*1093_*1096delATAT

Variant names:

• chr11-74456155-AATAT-A
• rs113583236
• NM_005472.5:c.*1093_*1096delATAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_005472.5(KCNE3):​c.*1093_*1096delATAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.017 (42 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: KCNE3 NM_005472.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0174 (1971/113062) while in subpopulation AFR AF = 0.0209 (721/34418). AF 95% confidence interval is 0.0197. There are 42 homozygotes in GnomAd4. There are 927 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1971 AD,Unknown gene.

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.*1093_*1096delATAT		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.*1093_*1096delATAT		3_prime_UTR	Exon 3 of 3	ENSP00000310557.4	Q9Y6H6
	KCNE3	ENST00000875764.1		c.*1093_*1096delATAT		3_prime_UTR	Exon 4 of 4	ENSP00000545823.1
	KCNE3	ENST00000929452.1		c.*1093_*1096delATAT		3_prime_UTR	Exon 4 of 4	ENSP00000599511.1

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 1973 AN: 113038 Hom.: 42 Cov.: 0

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.00384

Gnomad AMR AF: 0.00935

Gnomad ASJ AF: 0.00813

Gnomad EAS AF: 0.000926

Gnomad SAS AF: 0.0100

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.00901

Gnomad NFE AF: 0.0190

Gnomad OTH AF: 0.0169

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

GnomAD4 genome AF: 0.0174 AC: 1971 AN: 113062 Hom.: 42 Cov.: 0 AF XY: 0.0174 AC XY: 927 AN XY: 53300

African (AFR) AF: 0.0209 AC: 721 AN: 34418

American (AMR) AF: 0.00934 AC: 97 AN: 10388

Ashkenazi Jewish (ASJ) AF: 0.00813 AC: 23 AN: 2830

East Asian (EAS) AF: 0.000930 AC: 3 AN: 3226

South Asian (SAS) AF: 0.0101 AC: 33 AN: 3278

European-Finnish (FIN) AF: 0.0164 AC: 68 AN: 4150

Middle Eastern (MID) AF: 0.00952 AC: 2 AN: 210

European-Non Finnish (NFE) AF: 0.0190 AC: 996 AN: 52286

Other (OTH) AF: 0.0167 AC: 25 AN: 1494

Alfa AF: 0.00 Hom.: 640

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

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

Other links and lift over

dbSNP: rs113583236; hg19: chr11-74167200;