dbSNP rs779124360: KCNE1:p.Trp17* (chr21-34449585-C-T) – ACMG Classification: Likely_pathogenic (9 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1PP5

The NM_000219.6(KCNE1):c.50G>A(p.Trp17*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 13)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNE1
NM_000219.6 stop_gained

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.91

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

long QT syndrome 5
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
Jervell and Lange-Nielsen syndrome 2
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
Jervell and Lange-Nielsen syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
atrial fibrillation
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

KCNE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 20 pathogenic variants in the truncated region.

PP5

Variant 21-34449585-C-T is Pathogenic according to our data. Variant chr21-34449585-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 547163.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000219.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KCNE1	NM_000219.6	MANE Select	c.50G>A	p.Trp17*	stop_gained	Exon 4 of 4	NP_000210.2
KCNE1	NM_001127668.4		c.50G>A	p.Trp17*	stop_gained	Exon 3 of 3	NP_001121140.1
KCNE1	NM_001127669.4		c.50G>A	p.Trp17*	stop_gained	Exon 3 of 3	NP_001121141.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KCNE1	ENST00000399286.3	TSL:1 MANE Select	c.50G>A	p.Trp17*	stop_gained	Exon 4 of 4	ENSP00000382226.2
KCNE1	ENST00000399289.7	TSL:1	c.50G>A	p.Trp17*	stop_gained	Exon 3 of 3	ENSP00000382228.3
KCNE1	ENST00000416357.6	TSL:1	c.50G>A	p.Trp17*	stop_gained	Exon 2 of 2	ENSP00000416258.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251328

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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: AC0;AS_VQSR

AF:

0.00

AC:

AN:

908958

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

460276

African (AFR)

AF:

0.00

AC:

AN:

21238

American (AMR)

AF:

0.00

AC:

AN:

37226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19024

East Asian (EAS)

AF:

0.00

AC:

AN:

30798

South Asian (SAS)

AF:

0.00

AC:

AN:

63290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3956

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

651560

Other (OTH)

AF:

0.00

AC:

AN:

40234

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Jervell and Lange-Nielsen syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.55

BayesDel_noAF

Pathogenic

0.44

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.21

Eigen_PC

Benign

-0.017

FATHMM_MKL

Benign

0.66

PhyloP100

1.9

Vest4

0.77

GERP RS

1.1

Mutation Taster

=0/200

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over