11-74456329-CAAAAA-CAAAAAAA

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_005472.5(KCNE3):​c.*921_*922dupTT 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 0.0072 (14 hom., cov: 0)
  • Exomes 𝑓: 0.034 (0 hom.)
• Consequence: KCNE3 NM_005472.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554

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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00724 (874/120640) while in subpopulation AFR AF= 0.0256 (805/31418). AF 95% confidence interval is 0.0242. There are 14 homozygotes in gnomad4. There are 415 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 874 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00726 AC: 876 AN: 120654 Hom.: 14 Cov.: 0

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000822

Gnomad FIN AF: 0.000368

Gnomad MID AF: 0.00781

Gnomad NFE AF: 0.000240

Gnomad OTH AF: 0.00427

GnomAD4 exome AF: 0.0345 AC: 2 AN: 58 Hom.: 0 Cov.: 0 AF XY: 0.0238 AC XY: 1 AN XY: 42

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0400

GnomAD4 genome AF: 0.00724 AC: 874 AN: 120640 Hom.: 14 Cov.: 0 AF XY: 0.00727 AC XY: 415 AN XY: 57084

Gnomad4 AFR AF: 0.0256

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.000368

Gnomad4 NFE AF: 0.000223

Gnomad4 OTH AF: 0.00425

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;