chrX-109624598-C-A

Variant names:

• chrX-109624598-C-A
• NM_012282.4:c.423G>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_012282.4(KCNE5):​c.423G>T​(p.Arg141Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000201 in 995,416 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R141R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000020 (0 hom. 0 hem.)
• Consequence: KCNE5 NM_012282.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286

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]

ACSL4 (HGNC:3571): (acyl-CoA synthetase long chain family member 4) The protein encoded by this gene is an isozyme of the long-chain fatty-acid-coenzyme A ligase family. Although differing in substrate specificity, subcellular localization, and tissue distribution, all isozymes of this family convert free long-chain fatty acids into fatty acyl-CoA esters, and thereby play a key role in lipid biosynthesis and fatty acid degradation. This isozyme preferentially utilizes arachidonate as substrate. The absence of this enzyme may contribute to the cognitive disability or Alport syndrome. Alternative splicing of this gene generates multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-0.286 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNE5	NM_012282.4	c.423G>T	p.Arg141Arg	synonymous_variant	Exon 1 of 1	ENST00000372101.3	NP_036414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE5	ENST00000372101.3	c.423G>T	p.Arg141Arg	synonymous_variant	Exon 1 of 1	6	NM_012282.4	ENSP00000361173.2
ACSL4	ENST00000439581.1	n.387-277G>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000201 AC: 2 AN: 995416 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 317424

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000384

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.86
DANN	Benign	0.83

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: chrX-108867827;