X-48966157-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004979.6(KCND1):c.1616G>A(p.Arg539His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,209,422 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 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. R539C) has been classified as Uncertain significance.
Frequency
Consequence
NM_004979.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCND1 | ENST00000218176.4 | c.1616G>A | p.Arg539His | missense_variant | Exon 5 of 6 | 1 | NM_004979.6 | ENSP00000218176.3 | ||
KCND1 | ENST00000376477.5 | c.485G>A | p.Arg162His | missense_variant | Exon 4 of 5 | 2 | ENSP00000365660.1 | |||
KCND1 | ENST00000419374.1 | c.329G>A | p.Arg110His | missense_variant | Exon 2 of 2 | 3 | ENSP00000413989.1 |
Frequencies
GnomAD3 genomes AF: 0.0000265 AC: 3AN: 113128Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 35258
GnomAD3 exomes AF: 0.0000224 AC: 4AN: 178907Hom.: 0 AF XY: 0.0000155 AC XY: 1AN XY: 64619
GnomAD4 exome AF: 0.0000465 AC: 51AN: 1096294Hom.: 0 Cov.: 31 AF XY: 0.0000386 AC XY: 14AN XY: 362402
GnomAD4 genome AF: 0.0000265 AC: 3AN: 113128Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 35258
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1616G>A (p.R539H) alteration is located in exon 5 (coding exon 5) of the KCND1 gene. This alteration results from a G to A substitution at nucleotide position 1616, causing the arginine (R) at amino acid position 539 to be replaced by a histidine (H). 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