NM_080671.4:c.239G>T

Variant names:

• chr2-223053069-G-T
• rs761363201
• NM_080671.4:c.239G>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3 BS2

The NM_080671.4(KCNE4):​c.239G>T​(p.Trp80Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: KCNE4 NM_080671.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.51

Genes affected

KCNE4 (HGNC:6244): (potassium voltage-gated channel subfamily E regulatory subunit 4) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, isk-related subfamily. This member is a type I membrane protein, and a beta subunit that assembles with a potassium channel alpha-subunit to modulate the gating kinetics and enhance stability of the multimeric complex. This gene is prominently expressed in the embryo and in adult uterus. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.804
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNE4	NM_080671.4	c.239G>T	p.Trp80Leu	missense_variant	Exon 2 of 2	ENST00000281830.4	NP_542402.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE4	ENST00000281830.4	c.239G>T	p.Trp80Leu	missense_variant	Exon 2 of 2	1	NM_080671.4	ENSP00000281830.5
KCNE4	ENST00000488477.2	n.75+795G>T		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.0000359 AC: 9 AN: 251014 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135782

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461612 Hom.: 0 Cov.: 78 AF XY: 0.00000550 AC XY: 4 AN XY: 727102

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000157

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000282 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	0.0066	T
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.96
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.084	D
PrimateAI	Uncertain	0.57	T
REVEL	Uncertain	0.50
Sift4G	Pathogenic	0.0	D
Vest4		0.83
MVP		0.23
ClinPred		0.84	D
GERP RS		5.9
Varity_R		0.58
gMVP		0.63

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: rs761363201; hg19: chr2-223917787;