rs2270676

Variant names:

• chr11-74457366-A-C
• NM_005472.5:c.198T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-74457366-A-C
• chr11-74457366-A-G
• chr11-74457366-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005472.5(KCNE3):​c.198T>G​(p.Phe66Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F66F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNE3 NM_005472.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433

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]

ENSG00000254631 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17895639).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNE3	NM_005472.5	c.198T>G	p.Phe66Leu	missense_variant	Exon 3 of 3	ENST00000310128.9	NP_005463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE3	ENST00000310128.9	c.198T>G	p.Phe66Leu	missense_variant	Exon 3 of 3	1	NM_005472.5	ENSP00000310557.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.26	T;T;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.67	.;T;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.2	L;L;.
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	0.070	N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.60	T;T;T
Sift4G	Benign	0.66	T;T;.
Polyphen		0.025	B;B;.
Vest4		0.17
MutPred		0.36		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.91
MPC		0.24
ClinPred		0.10	T
GERP RS		1.2
Varity_R		0.38
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-74168411;