3-19342635-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_144633.3(KCNH8):c.491G>A(p.Arg164Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000168 in 1,610,750 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R164W) has been classified as Uncertain significance.
Frequency
Consequence
NM_144633.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNH8 | NM_144633.3 | c.491G>A | p.Arg164Gln | missense_variant | 4/16 | ENST00000328405.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNH8 | ENST00000328405.7 | c.491G>A | p.Arg164Gln | missense_variant | 4/16 | 1 | NM_144633.3 | P1 | |
KCNH8 | ENST00000452398.5 | c.491G>A | p.Arg164Gln | missense_variant, NMD_transcript_variant | 4/16 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152090Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000360 AC: 9AN: 250166Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135208
GnomAD4 exome AF: 0.0000158 AC: 23AN: 1458660Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 725734
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152090Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74294
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 05, 2023 | The c.491G>A (p.R164Q) alteration is located in exon 4 (coding exon 4) of the KCNH8 gene. This alteration results from a G to A substitution at nucleotide position 491, causing the arginine (R) at amino acid position 164 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at