chr11-74455736-G-GTT

Variant names:

• chr11-74455736-G-GTT
• rs41315535
• NM_005472.5:c.*1514_*1515dupAA

Variant summary

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

The NM_005472.5(KCNE3):​c.*1514_*1515dupAA 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 0.085 (620 hom., cov: 0)
  • Exomes 𝑓: 0.079 (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-GTT is Benign according to our data. Variant chr11-74455736-G-GTT is described in ClinVar as Likely_benign. ClinVar VariationId is 306041.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0937 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.*1514_*1515dupAA		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.*1514_*1515dupAA		3_prime_UTR	Exon 3 of 3	ENSP00000310557.4	Q9Y6H6
	KCNE3	ENST00000875764.1		c.*1514_*1515dupAA		3_prime_UTR	Exon 4 of 4	ENSP00000545823.1
	KCNE3	ENST00000929452.1		c.*1514_*1515dupAA		3_prime_UTR	Exon 4 of 4	ENSP00000599511.1

Frequencies

GnomAD3 genomes AF: 0.0854 AC: 12694 AN: 148682 Hom.: 619 Cov.: 0

Gnomad AFR AF: 0.0797

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.000795

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.0641

Gnomad MID AF: 0.125

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.0976

GnomAD4 exome AF: 0.0789 AC: 3 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: 0.00 AC: 0 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: 0.100 AC: 3 AN: 30

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

GnomAD4 genome AF: 0.0854 AC: 12706 AN: 148788 Hom.: 620 Cov.: 0 AF XY: 0.0831 AC XY: 6028 AN XY: 72502

African (AFR) AF: 0.0800 AC: 3225 AN: 40318

American (AMR) AF: 0.0904 AC: 1353 AN: 14962

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 584 AN: 3436

East Asian (EAS) AF: 0.000797 AC: 4 AN: 5020

South Asian (SAS) AF: 0.0218 AC: 102 AN: 4678

European-Finnish (FIN) AF: 0.0641 AC: 639 AN: 9964

Middle Eastern (MID) AF: 0.114 AC: 33 AN: 290

European-Non Finnish (NFE) AF: 0.0957 AC: 6428 AN: 67196

Other (OTH) AF: 0.0962 AC: 195 AN: 2028

Alfa AF: 0.0284 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

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

Other links and lift over

dbSNP: rs41315535; hg19: chr11-74166781;