rs199473647

Positions:

• chr21-34449256-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000219.6(KCNE1):​c.379C>A​(p.Pro127Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNE1 NM_000219.6 missense
• Clinical Significance: not provided no classification provided O:2
• Conservation: PhyloP100: 1.33

Genes affected

KCNE1 (HGNC:6240): (potassium voltage-gated channel subfamily E regulatory subunit 1) The product of this gene belongs to the potassium channel KCNE family. Potassium ion channels are essential to many cellular functions and show a high degree of diversity, varying in their electrophysiologic and pharmacologic properties. This gene encodes a transmembrane protein known to associate with the product of the KVLQT1 gene to form the delayed rectifier potassium channel. Mutation in this gene are associated with both Jervell and Lange-Nielsen and Romano-Ward forms of long-QT syndrome. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2428573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNE1	NM_000219.6	c.379C>A	p.Pro127Thr	missense_variant	4/4	ENST00000399286.3	NP_000210.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNE1	ENST00000399286.3	c.379C>A	p.Pro127Thr	missense_variant	4/4	1	NM_000219.6	ENSP00000382226.2

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 832068 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 430014

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 16

ClinVar

Significance: not provided

Submissions summary: Other:2

Revision: no classification provided

Submissions by phenotype

Long QT syndrome 5 Other:1

not provided, no classification provided

in vitro

Roden Lab, Vanderbilt University Medical Center

-

- -

Congenital long QT syndrome Other:1

not provided, no classification provided

literature only

Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust

-

This variant has been reported as associated with Long QT syndrome in the following publications (PMID:10973849;PMID:15051636). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Uncertain	0.64	D;D;D;D;D;D;D;D
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.47	.;.;T;.;.;.;.;.
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.24	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Uncertain	2.5	M;M;M;M;M;M;M;M
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.35	N;.;.;N;N;N;N;N
REVEL	Uncertain	0.59
Sift	Uncertain	0.010	D;.;.;D;D;D;D;D
Sift4G	Uncertain	0.022	D;D;D;D;D;D;D;D
Polyphen		0.024	B;B;B;B;B;B;B;B
Vest4		0.11
MutPred		0.37		Gain of phosphorylation at P127 (P = 0.0295);Gain of phosphorylation at P127 (P = 0.0295);Gain of phosphorylation at P127 (P = 0.0295);Gain of phosphorylation at P127 (P = 0.0295);Gain of phosphorylation at P127 (P = 0.0295);Gain of phosphorylation at P127 (P = 0.0295);Gain of phosphorylation at P127 (P = 0.0295);Gain of phosphorylation at P127 (P = 0.0295);
MVP		0.87
MPC		0.14
ClinPred		0.11	T
GERP RS		0.67
Varity_R		0.042
gMVP		0.30

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

Other links and lift over

dbSNP: rs199473647; hg19: chr21-35821554;