rs17221826
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_005472.5(KCNE3):c.228C>T(p.Ile76=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,614,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000047 ( 0 hom. )
Consequence
KCNE3
NM_005472.5 synonymous
NM_005472.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.25
Genes affected
KCNE3 (HGNC:6243): (potassium voltage-gated channel subfamily E regulatory subunit 3) 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 kidney. A missense mutation in this gene is associated with hypokalemic periodic paralysis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant 11-74457336-G-A is Benign according to our data. Variant chr11-74457336-G-A is described in ClinVar as [Benign]. Clinvar id is 698783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.25 with no splicing effect.
BS2
?
High AC in GnomAd at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNE3 | NM_005472.5 | c.228C>T | p.Ile76= | synonymous_variant | 3/3 | ENST00000310128.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNE3 | ENST00000310128.9 | c.228C>T | p.Ile76= | synonymous_variant | 3/3 | 1 | NM_005472.5 | P1 | |
KCNE3 | ENST00000525550.1 | c.228C>T | p.Ile76= | synonymous_variant | 2/2 | 1 | P1 | ||
ENST00000533008.1 | n.155-26841G>A | intron_variant, non_coding_transcript_variant | 3 | ||||||
KCNE3 | ENST00000532569.5 | c.228C>T | p.Ile76= | synonymous_variant | 3/3 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152208Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000243 AC: 61AN: 251340Hom.: 0 AF XY: 0.000199 AC XY: 27AN XY: 135858
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GnomAD4 exome AF: 0.0000465 AC: 68AN: 1461876Hom.: 0 Cov.: 30 AF XY: 0.0000358 AC XY: 26AN XY: 727242
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GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152326Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74494
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 11, 2020 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Brugada syndrome 6 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 07, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at