chrX-109623948-G-A

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

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]

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNE5	NM_012282.4	c.*644C>T		3_prime_UTR_variant	Exon 1 of 1	ENST00000372101.3	NP_036414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE5	ENST00000372101	c.*644C>T		3_prime_UTR_variant	Exon 1 of 1		NM_012282.4	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

Gnomad4 AFR exome AF: 1.00 AC: 3 AN: 3

Gnomad4 AMR exome AC: 0 AN: 0

Gnomad4 ASJ exome AC: 0 AN: 0

Gnomad4 EAS exome AC: 0 AN: 0

Gnomad4 SAS exome AC: 0 AN: 0

Gnomad4 FIN exome AF: 0.714 AC: 5 AN: 7

Gnomad4 NFE exome AF: 0.690 AC: 20 AN: 29

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.887 AC: 0.88694 AN: 0.88694

Gnomad4 AMR AF: 0.767 AC: 0.766546 AN: 0.766546

Gnomad4 ASJ AF: 0.646 AC: 0.64623 AN: 0.64623

Gnomad4 EAS AF: 0.919 AC: 0.919332 AN: 0.919332

Gnomad4 SAS AF: 0.750 AC: 0.749509 AN: 0.749509

Gnomad4 FIN AF: 0.506 AC: 0.506346 AN: 0.506346

Gnomad4 NFE AF: 0.614 AC: 0.61438 AN: 0.61438

Gnomad4 OTH AF: 0.722 AC: 0.72178 AN: 0.72178

Alfa AF: 0.670 Hom.: 42287

Bravo AF: 0.743

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.74
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

Publications

LitVar

Other links and lift over

dbSNP: rs697829; hg19: chrX-108867177;