Genetic Variant NM_000219.6:c.235A>G (chr21-34449400-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_000219.6(KCNE1):c.235A>G(p.Asn79Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as not provided (no stars). Synonymous variant affecting the same amino acid position (i.e. N79N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 17)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNE1
NM_000219.6 missense

Scores

Clinical Significance

not provided no classification provided O:2

Conservation

PhyloP100: 3.33

Variant links:

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]

KCNE1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNE1	NM_000219.6 link	c.235A>G	p.Asn79Asp	missense_variant	Exon 4 of 4	ENST00000399286.3	NP_000210.2	P15382C7S316Q6FHJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE1	ENST00000399286.3 link	c.235A>G	p.Asn79Asp	missense_variant	Exon 4 of 4	1	NM_000219.6	ENSP00000382226.2		P15382

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251436

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.85e-7

AC:

AN:

1459138

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726026

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: not provided

Submissions summary: Other:2

Revision: no classification provided

LINK: link

Submissions by phenotype

Long QT syndrome 5

Other:1

Roden Lab, Vanderbilt University Medical Center

Significance: not provided

Review Status: no classification provided

Collection Method: in vitro

- -

not provided

Other:1

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

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

This variant has been reported in the following publications (PMID:10428953). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.93

D;D;D;D;D;D;D;D

Eigen

Uncertain

0.33

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.72

.;.;T;.;.;.;.;.

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.70

D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

0.85

MutationAssessor

Uncertain

2.8

M;M;M;M;M;M;M;M

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.5

N;.;.;N;N;N;N;N

REVEL

Pathogenic

0.67

Sift

Benign

0.038

D;.;.;D;D;D;D;D

Sift4G

Benign

0.075

T;T;T;T;T;T;T;T

Polyphen

0.98

D;D;D;D;D;D;D;D

Vest4

0.51

MutPred

0.49

Gain of disorder (P = 0.1326);Gain of disorder (P = 0.1326);Gain of disorder (P = 0.1326);Gain of disorder (P = 0.1326);Gain of disorder (P = 0.1326);Gain of disorder (P = 0.1326);Gain of disorder (P = 0.1326);Gain of disorder (P = 0.1326);

MVP

0.93

MPC

0.22

ClinPred

0.78

GERP RS

4.0

Varity_R

0.27

gMVP

0.78

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