11-74456329-CAAAAA-CAAA

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

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. 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

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]

ENSG00000254928 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNE3	NM_005472.5	c.*921_*922delTT		3_prime_UTR_variant	Exon 3 of 3	ENST00000310128.9	NP_005463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE3	ENST00000310128	c.*921_*922delTT		3_prime_UTR_variant	Exon 3 of 3	1	NM_005472.5	ENSP00000310557.4
ENSG00000254928	ENST00000530510.1	n.426-301_426-300delAA		intron_variant	Intron 1 of 1	2
ENSG00000254631	ENST00000533008.1	n.155-27836_155-27835delAA		intron_variant	Intron 2 of 3	3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0208

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

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000479

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000368

Gnomad4 NFE AF: 0.0000515

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs60016728; hg19: chr11-74167374;