chr11-74456155-A-AATATATATATATAT

Position:

• chr11-74456155-A-AATATATATATATAT

Variant summary

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

The NM_005472.5(KCNE3):​c.*1083_*1096dupATATATATATATAT 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 0.062 (433 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: KCNE3 NM_005472.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 (NFE) allele frequency at 95% confidence interval = 0.0897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNE3	NM_005472.5	c.*1083_*1096dupATATATATATATAT		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.*1083_*1096dupATATATATATATAT		3_prime_UTR_variant	3/3	1	NM_005472.5	ENSP00000310557.4
ENSG00000254928	ENST00000530510.1	n.425+395_425+408dupTATATATATATATA		intron_variant		2
ENSG00000254631	ENST00000533008.1	n.155-28010_155-27997dupTATATATATATATA		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0622 AC: 6999 AN: 112518 Hom.: 433 Cov.: 0

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.0641

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0297

Gnomad SAS AF: 0.0808

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.0623

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0622 AC: 7003 AN: 112542 Hom.: 433 Cov.: 0 AF XY: 0.0597 AC XY: 3168 AN XY: 53030

Gnomad4 AFR AF: 0.0212

Gnomad4 AMR AF: 0.0459

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0299

Gnomad4 SAS AF: 0.0818

Gnomad4 FIN AF: 0.0466

Gnomad4 NFE AF: 0.0919

Gnomad4 OTH AF: 0.0624

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: rs113583236; hg19: chr11-74167200;