11-74456329-C-CAAA

Position:

• chr11-74456329-C-CAAA

Variant summary

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

The NM_005472.5(KCNE3):​c.*920_*922dupTTT 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 0.22 (3672 hom., cov: 0)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: KCNE3 NM_005472.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• 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.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNE3	NM_005472.5	c.*920_*922dupTTT		3_prime_UTR_variant	3/3	ENST00000310128.9	NP_005463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNE3	ENST00000310128	c.*920_*922dupTTT		3_prime_UTR_variant	3/3	1	NM_005472.5	ENSP00000310557.4
ENSG00000254928	ENST00000530510.1	n.426-302_426-300dupAAA		intron_variant		2
ENSG00000254631	ENST00000533008.1	n.155-27837_155-27835dupAAA		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 25925 AN: 120074 Hom.: 3666 Cov.: 0

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0730

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.103 AC: 6 AN: 58 Hom.: 0 Cov.: 0 AF XY: 0.0714 AC XY: 3 AN XY: 42

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0800

GnomAD4 genome AF: 0.216 AC: 25935 AN: 120060 Hom.: 3672 Cov.: 0 AF XY: 0.214 AC XY: 12173 AN XY: 56824

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.0728

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.202

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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;