chr21-34449523-T-G

Position:

• 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>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 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=0.10619265).

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	ENSP00000382226.2

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
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;