rs697829

Variant names:

• chrX-109623948-G-A
• rs697829
• NM_012282.4:c.*644C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012282.4(KCNE5):​c.*644C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.71 (20761 hom., 22949 hem., cov: 22)
  • Exomes 𝑓: 0.73 (6 hom. 17 hem.)
  • Failed GnomAD Quality Control
• Consequence: KCNE5 NM_012282.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.836
• Publications: 8 publications found

Genes affected

KCNE5 (HGNC:6241): (potassium voltage-gated channel subfamily E regulatory subunit 5) This gene encodes a member of a family of single pass transmembrane domain proteins that function as ancillary subunits to voltage-gated potassium channels. Members of this family affect diverse processes in potassium channel regulation, including ion selectivity, voltage dependence, and anterograde recycling from the plasma membrane. Variants of this gene are associated with idiopathic ventricular fibrillation and Brugada syndrome. [provided by RefSeq, Nov 2016]

KCNE5 Gene-Disease associations (from GenCC):

• Brugada syndrome

  Inheritance: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Genomics England PanelApp, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012282.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE5	NM_012282.4	MANE Select	c.*644C>T		3_prime_UTR	Exon 1 of 1	NP_036414.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE5	ENST00000372101.3	TSL:6 MANE Select	c.*644C>T		3_prime_UTR	Exon 1 of 1	ENSP00000361173.2

Frequencies

GnomAD3 genomes AF: 0.714 AC: 78703 AN: 110171 Hom.: 20763 Cov.: 22

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.722

GnomAD4 exome AF: 0.729 AC: 35 AN: 48 Hom.: 6 Cov.: 0 AF XY: 0.850 AC XY: 17 AN XY: 20

African (AFR) AF: 1.00 AC: 3 AN: 3

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.714 AC: 5 AN: 7

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.690 AC: 20 AN: 29

Other (OTH) AF: 0.778 AC: 7 AN: 9

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.714 AC: 78754 AN: 110226 Hom.: 20761 Cov.: 22 AF XY: 0.707 AC XY: 22949 AN XY: 32454

African (AFR) AF: 0.887 AC: 26806 AN: 30223

American (AMR) AF: 0.767 AC: 8061 AN: 10516

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 1697 AN: 2626

East Asian (EAS) AF: 0.919 AC: 3191 AN: 3471

South Asian (SAS) AF: 0.750 AC: 1909 AN: 2547

European-Finnish (FIN) AF: 0.506 AC: 2952 AN: 5830

Middle Eastern (MID) AF: 0.765 AC: 166 AN: 217

European-Non Finnish (NFE) AF: 0.614 AC: 32325 AN: 52614

Other (OTH) AF: 0.722 AC: 1087 AN: 1506

Alfa AF: 0.670 Hom.: 42287

Bravo AF: 0.743

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.74
PhyloP100		0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs697829; hg19: chrX-108867177;