11-74456329-C-CAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005472.5(KCNE3):c.*922_*923insTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.070 (342 hom., cov: 0)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: KCNE3 NM_005472.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNE3	NM_005472.5	c.*922_*923insTTTT		3_prime_UTR_variant	3/3	ENST00000310128.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNE3	ENST00000310128.9	c.*922_*923insTTTT		3_prime_UTR_variant	3/3	1	NM_005472.5	P1
	ENST00000530510.1	n.426-303_426-300dup		intron_variant, non_coding_transcript_variant		2
	ENST00000533008.1	n.155-27838_155-27835dup		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 8471 AN: 120426 Hom.: 343 Cov.: 0

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.0514

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0822

Gnomad OTH AF: 0.0665

GnomAD4 exome AF: 0.172 AC: 10 AN: 58 Hom.: 0 Cov.: 0 AF XY: 0.214 AC XY: 9 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: 0.200

GnomAD4 genome AF: 0.0703 AC: 8460 AN: 120414 Hom.: 342 Cov.: 0 AF XY: 0.0730 AC XY: 4158 AN XY: 56960

Gnomad4 AFR AF: 0.0395

Gnomad4 AMR AF: 0.0513

Gnomad4 ASJ AF: 0.0671

Gnomad4 EAS AF: 0.0690

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0822

Gnomad4 OTH AF: 0.0657

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Brugada syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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;