Variant 11-74457254-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005472.5(KCNE3):c.310T>C(p.Ter104GlnextTer62) variant causes a stop lost change. The variant allele was found at a frequency of 0.000000684 in 1,461,442 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KCNE3
NM_005472.5 stop_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11

Variant links:

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]

KCNE3 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNE3	NM_005472.5 linkuse as main transcript	c.310T>C	p.Ter104GlnextTer62	stop_lost	3/3	ENST00000310128.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
KCNE3	ENST00000310128.9 linkuse as main transcript	c.310T>C	p.Ter104GlnextTer62	stop_lost	3/3	1	NM_005472.5	P1
KCNE3	ENST00000525550.1 linkuse as main transcript	c.310T>C	p.Ter104GlnextTer?	stop_lost	2/2	1		P1
	ENST00000533008.1 linkuse as main transcript	n.155-26923A>G		intron_variant, non_coding_transcript_variant		3
KCNE3	ENST00000532569.5 linkuse as main transcript			downstream_gene_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461442

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727010

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Brugada syndrome 6

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Oct 27, 2017

This sequence change disrupts the translational stop signal of the KCNE3 mRNA. It is expected to extend the length of the KCNE3 protein by 62 additional amino acid residues. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with KCNE3-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the additional amino acids are currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.21

Cadd

Benign

Dann

Benign

0.81

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.89

FATHMM_MKL

Pathogenic

0.99

MutationTaster

Benign

1.0

N;N

Vest4

0.070

GERP RS

5.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over