11-74456329-CAAAAA-CAAAAAAAAAA

Variant names:

• chr11-74456329-C-CAAAAA
• rs60016728
• NM_005472.5:c.*918_*922dupTTTTT

Variant summary

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

The NM_005472.5(KCNE3):​c.*918_*922dupTTTTT 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 0.021 (99 hom., cov: 0)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: KCNE3 NM_005472.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0727 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.*918_*922dupTTTTT		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.*918_*922dupTTTTT		3_prime_UTR	Exon 3 of 3	ENSP00000310557.4	Q9Y6H6
	KCNE3	ENST00000875764.1		c.*918_*922dupTTTTT		3_prime_UTR	Exon 4 of 4	ENSP00000545823.1
	KCNE3	ENST00000929452.1		c.*918_*922dupTTTTT		3_prime_UTR	Exon 4 of 4	ENSP00000599511.1

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 2524 AN: 120576 Hom.: 100 Cov.: 0

Gnomad AFR AF: 0.0754

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00843

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.000822

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00391

Gnomad NFE AF: 0.000377

Gnomad OTH AF: 0.0159

GnomAD4 exome AF: 0.172 AC: 10 AN: 58 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 7 AN XY: 42

African (AFR) AF: 0.250 AC: 1 AN: 4

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

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 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: 0.140 AC: 7 AN: 50

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0209 AC: 2523 AN: 120562 Hom.: 99 Cov.: 0 AF XY: 0.0208 AC XY: 1185 AN XY: 57052

African (AFR) AF: 0.0753 AC: 2360 AN: 31350

American (AMR) AF: 0.00842 AC: 100 AN: 11880

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3112

East Asian (EAS) AF: 0.00289 AC: 12 AN: 4156

South Asian (SAS) AF: 0.000552 AC: 2 AN: 3624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5442

Middle Eastern (MID) AF: 0.00417 AC: 1 AN: 240

European-Non Finnish (NFE) AF: 0.000377 AC: 22 AN: 58298

Other (OTH) AF: 0.0158 AC: 26 AN: 1646

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs60016728; hg19: chr11-74167374;