11-74455736-GT-GTT

Variant names:

• chr11-74455736-G-GT
• rs41315535
• NM_005472.5:c.*1515dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005472.5(KCNE3):​c.*1515dupA 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
• Publications: 1 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 -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 VariationId 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.

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.*1515dupA		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.*1515dupA		3_prime_UTR	Exon 3 of 3	ENSP00000310557.4	Q9Y6H6
	KCNE3	ENST00000875764.1		c.*1515dupA		3_prime_UTR	Exon 4 of 4	ENSP00000545823.1
	KCNE3	ENST00000929452.1		c.*1515dupA		3_prime_UTR	Exon 4 of 4	ENSP00000599511.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

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) AF: 0.0333 AC: 1 AN: 30

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.492 AC: 19822 AN: 40300

American (AMR) AF: 0.137 AC: 2050 AN: 14966

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 433 AN: 3436

East Asian (EAS) AF: 0.157 AC: 787 AN: 5018

South Asian (SAS) AF: 0.288 AC: 1347 AN: 4672

European-Finnish (FIN) AF: 0.226 AC: 2251 AN: 9964

Middle Eastern (MID) AF: 0.210 AC: 61 AN: 290

European-Non Finnish (NFE) AF: 0.122 AC: 8207 AN: 67190

Other (OTH) AF: 0.197 AC: 400 AN: 2030

Alfa AF: 0.0729 Hom.: 72

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Brugada syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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: rs41315535; hg19: chr11-74166781;