NM_005472.5:c.*921_*922delTT

Variant names:

• chr11-74456329-CAA-C
• rs60016728
• NM_005472.5:c.*921_*922delTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005472.5(KCNE3):​c.*921_*922delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000663 in 120,700 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000058 (0 hom., cov: 0)
  • Exomes 𝑓: 0.018 (0 hom.)
• Consequence: KCNE3 NM_005472.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.*921_*922delTT		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.*921_*922delTT		3_prime_UTR	Exon 3 of 3	ENSP00000310557.4	Q9Y6H6
	KCNE3	ENST00000875764.1		c.*921_*922delTT		3_prime_UTR	Exon 4 of 4	ENSP00000545823.1
	KCNE3	ENST00000929452.1		c.*921_*922delTT		3_prime_UTR	Exon 4 of 4	ENSP00000599511.1

Frequencies

GnomAD3 genomes AF: 0.0000580 AC: 7 AN: 120644 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000479

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000368

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000515

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0179 AC: 1 AN: 56 Hom.: 0 AF XY: 0.0250 AC XY: 1 AN XY: 40

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 4

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: 0.0208 AC: 1 AN: 48

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000580 AC: 7 AN: 120644 Hom.: 0 Cov.: 0 AF XY: 0.0000350 AC XY: 2 AN XY: 57070

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31386

American (AMR) AF: 0.00 AC: 0 AN: 11870

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

East Asian (EAS) AF: 0.000479 AC: 2 AN: 4172

South Asian (SAS) AF: 0.00 AC: 0 AN: 3650

European-Finnish (FIN) AF: 0.000368 AC: 2 AN: 5440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.0000515 AC: 3 AN: 58304

Other (OTH) AF: 0.00 AC: 0 AN: 1640

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000157175), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.34
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: rs60016728; hg19: chr11-74167374;