X-48966670-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting
The NM_004979.6(KCND1):c.1375G>A(p.Gly459Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,096,396 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 -3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCND1 | ENST00000218176.4 | c.1375G>A | p.Gly459Ser | missense_variant | 4/6 | 1 | NM_004979.6 | ENSP00000218176.3 | ||
KCND1 | ENST00000376477.5 | c.244G>A | p.Gly82Ser | missense_variant | 3/5 | 2 | ENSP00000365660.1 | |||
KCND1 | ENST00000419374.1 | c.88G>A | p.Gly30Ser | missense_variant | 1/2 | 3 | ENSP00000413989.1 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 exomes AF: 0.00000556 AC: 1AN: 179755Hom.: 0 AF XY: 0.0000155 AC XY: 1AN XY: 64443
GnomAD4 exome AF: 0.0000146 AC: 16AN: 1096396Hom.: 0 Cov.: 30 AF XY: 0.0000249 AC XY: 9AN XY: 361828
GnomAD4 genome Cov.: 22
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 03, 2021 | The c.1375G>A (p.G459S) alteration is located in exon 4 (coding exon 4) of the KCND1 gene. This alteration results from a G to A substitution at nucleotide position 1375, causing the glycine (G) at amino acid position 459 to be replaced by a serine (S). 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