11-74456155-AATATAT-A

Position:

• chr11-74456155-AATATAT-A

Variant summary

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

The NM_005472.5(KCNE3):​c.*1091_*1096delATATAT 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 0.60 (19182 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: KCNE3 NM_005472.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.296

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 (SAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNE3	NM_005472.5	c.*1091_*1096delATATAT		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.*1091_*1096delATATAT		3_prime_UTR_variant	3/3	1	NM_005472.5	ENSP00000310557.4
ENSG00000254928	ENST00000530510.1	n.425+403_425+408delTATATA		intron_variant		2
ENSG00000254631	ENST00000533008.1	n.155-28002_155-27997delTATATA		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.599 AC: 67758 AN: 113038 Hom.: 19178 Cov.: 0

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.613

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.599 AC: 67767 AN: 113062 Hom.: 19182 Cov.: 0 AF XY: 0.612 AC XY: 32648 AN XY: 53316

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.616

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Brugada syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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: rs113583236; hg19: chr11-74167200;