chrX-109624675-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_012282.4(KCNE5):c.346G>A(p.Ala116Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000742 in 1,172,844 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A116S) has been classified as Uncertain significance.
Frequency
Consequence
NM_012282.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNE5 | NM_012282.4 | c.346G>A | p.Ala116Thr | missense_variant | 1/1 | ENST00000372101.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNE5 | ENST00000372101.3 | c.346G>A | p.Ala116Thr | missense_variant | 1/1 | NM_012282.4 | P1 | ||
ACSL4 | ENST00000439581.1 | n.387-354G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000406 AC: 46AN: 113281Hom.: 0 Cov.: 25 AF XY: 0.000282 AC XY: 10AN XY: 35447
GnomAD3 exomes AF: 0.0000545 AC: 6AN: 110050Hom.: 0 AF XY: 0.0000297 AC XY: 1AN XY: 33716
GnomAD4 exome AF: 0.0000387 AC: 41AN: 1059563Hom.: 0 Cov.: 30 AF XY: 0.0000349 AC XY: 12AN XY: 343851
GnomAD4 genome ? AF: 0.000406 AC: 46AN: 113281Hom.: 0 Cov.: 25 AF XY: 0.000282 AC XY: 10AN XY: 35447
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 08, 2023 | The c.346G>A (p.A116T) alteration is located in exon 1 (coding exon 1) of the KCNE5 gene. This alteration results from a G to A substitution at nucleotide position 346, causing the alanine (A) at amino acid position 116 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 10, 2021 | Has not been previously published as pathogenic or benign to our knowledge - |
Brugada syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at