rs1805127

Variant names:

• chr21-34449523-T-A
• NM_000219.6:c.112A>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_000219.6(KCNE1):​c.112A>T​(p.Ser38Cys) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S38G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 12)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNE1 NM_000219.6 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=0.19347385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNE1	NM_000219.6	c.112A>T	p.Ser38Cys	missense_variant	Exon 4 of 4	ENST00000399286.3	NP_000210.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE1	ENST00000399286.3	c.112A>T	p.Ser38Cys	missense_variant	Exon 4 of 4	1	NM_000219.6	ENSP00000382226.2

Frequencies

GnomAD3 genomes Cov.: 12

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 844042 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	0.0059	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Uncertain	0.76	D;D;D;D;D;D;D;D
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.16	.;.;T;.;.;.;.;.
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	0.34	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.1	N;.;.;N;N;N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.032	D;.;.;D;D;D;D;D
Sift4G	Uncertain	0.058	T;T;T;T;T;T;T;T
Polyphen		0.23	B;B;B;B;B;B;B;B
Vest4		0.077
MutPred		0.27		Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);
MVP		0.70
MPC		0.22
ClinPred		0.15	T
GERP RS		0.18
Varity_R		0.098
gMVP		0.49

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: chr21-35821821;