NM_012282.4:c.423G>A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_012282.4(KCNE5):c.423G>A(p.Arg141Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000018 in 1,108,195 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 25)
Exomes 𝑓: 0.0000010 ( 0 hom. 1 hem. )
Consequence
KCNE5
NM_012282.4 synonymous
NM_012282.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.286
Publications
0 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]
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]
ACSL4 Gene-Disease associations (from GenCC):
- non-syndromic X-linked intellectual disabilityInheritance: XL Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Illumina, ClinGen, Orphanet
- intellectual disability, X-linked 63Inheritance: XL Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant X-109624598-C-T is Benign according to our data. Variant chrX-109624598-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1738980.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.286 with no splicing effect.
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.
Frequencies
GnomAD3 genomes 0.00000887 AC: 1AN: 112781Hom.: 0 Cov.: 25 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
112781
Hom.:
Cov.:
25
Gnomad AFR
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GnomAD2 exomes AF: 0.00 AC: 0AN: 53623 AF XY: 0.00
GnomAD2 exomes
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AC:
0
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53623
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Gnomad AFR exome
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GnomAD4 exome AF: 0.00000100 AC: 1AN: 995414Hom.: 0 Cov.: 30 AF XY: 0.00000315 AC XY: 1AN XY: 317424 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
995414
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
317424
show subpopulations
African (AFR)
AF:
AC:
0
AN:
21592
American (AMR)
AF:
AC:
0
AN:
16020
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
14732
East Asian (EAS)
AF:
AC:
0
AN:
26014
South Asian (SAS)
AF:
AC:
0
AN:
41323
European-Finnish (FIN)
AF:
AC:
0
AN:
34021
Middle Eastern (MID)
AF:
AC:
0
AN:
3185
European-Non Finnish (NFE)
AF:
AC:
1
AN:
796788
Other (OTH)
AF:
AC:
0
AN:
41739
GnomAD4 genome 0.00000887 AC: 1AN: 112781Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 34971 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
112781
Hom.:
Cov.:
25
AF XY:
AC XY:
0
AN XY:
34971
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
31108
American (AMR)
AF:
AC:
0
AN:
10817
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2652
East Asian (EAS)
AF:
AC:
0
AN:
3518
South Asian (SAS)
AF:
AC:
0
AN:
2793
European-Finnish (FIN)
AF:
AC:
0
AN:
6242
Middle Eastern (MID)
AF:
AC:
0
AN:
235
European-Non Finnish (NFE)
AF:
AC:
1
AN:
53206
Other (OTH)
AF:
AC:
0
AN:
1530
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
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2
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0.95
Allele balance
Alfa
AF:
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ClinVar
ClinVar submissions
View on ClinVar Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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