rs1805127

Positions:

• chr21-34449523-T-G
• chr21-34449523-T-C

Variant summary

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

The ENST00000399286.3(KCNE1):​c.112A>C​(p.Ser38Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S38D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 12)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNE1 ENST00000399286.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=0.10619265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNE1	NM_000219.6	c.112A>C	p.Ser38Arg	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.112A>C	p.Ser38Arg	missense_variant	4/4	1	NM_000219.6	ENSP00000382226	P1

Frequencies

GnomAD3 genomes Cov.: 12

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 844044 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 419742

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.: 12

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.0042	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	7.2
DANN	Benign	0.93
DEOGEN2	Uncertain	0.56	D;D;D;D;D;D;D;D
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.17	.;.;T;.;.;.;.;.
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.11	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.34	N;N;N;N;N;N;N;N
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N;.;.;N;N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.24	T;.;.;T;T;T;T;T
Sift4G	Benign	0.51	T;T;T;T;T;T;T;T
Polyphen		0.0030	B;B;B;B;B;B;B;B
Vest4		0.058
MutPred		0.20		Gain of solvent accessibility (P = 0.0155);Gain of solvent accessibility (P = 0.0155);Gain of solvent accessibility (P = 0.0155);Gain of solvent accessibility (P = 0.0155);Gain of solvent accessibility (P = 0.0155);Gain of solvent accessibility (P = 0.0155);Gain of solvent accessibility (P = 0.0155);Gain of solvent accessibility (P = 0.0155);
MVP		0.57
MPC		0.093
ClinPred		0.039	T
GERP RS		0.18
Varity_R		0.071
gMVP		0.46

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: rs1805127; hg19: chr21-35821821;