chr11-74455736-G-GTT

Position:

• chr11-74455736-G-GTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005472.5(KCNE3):​c.*1514_*1515dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.085 (620 hom., cov: 0)
  • Exomes 𝑓: 0.079 (0 hom.)
• Consequence: KCNE3 NM_005472.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.519

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 -10 ACMG points.

• BP6: Variant 11-74455736-G-GTT is Benign according to our data. Variant chr11-74455736-G-GTT is described in ClinVar as [Likely_benign]. Clinvar id is 306041.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNE3	NM_005472.5	c.*1514_*1515dupAA		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.*1514_*1515dupAA		3_prime_UTR_variant	3/3	1	NM_005472.5	ENSP00000310557.4
ENSG00000254928	ENST00000530510.1	n.397_398dupTT		non_coding_transcript_exon_variant	1/2	2
ENSG00000254631	ENST00000533008.1	n.155-28433_155-28432dupTT		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0854 AC: 12694 AN: 148682 Hom.: 619 Cov.: 0

Gnomad AFR AF: 0.0797

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.000795

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.0641

Gnomad MID AF: 0.125

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.0976

GnomAD4 exome AF: 0.0789 AC: 3 AN: 38 Hom.: 0 Cov.: 0 AF XY: 0.0625 AC XY: 2 AN XY: 32

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0854 AC: 12706 AN: 148788 Hom.: 620 Cov.: 0 AF XY: 0.0831 AC XY: 6028 AN XY: 72502

Gnomad4 AFR AF: 0.0800

Gnomad4 AMR AF: 0.0904

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.000797

Gnomad4 SAS AF: 0.0218

Gnomad4 FIN AF: 0.0641

Gnomad4 NFE AF: 0.0957

Gnomad4 OTH AF: 0.0962

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Brugada syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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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: rs41315535; hg19: chr11-74166781;