chr1-111776103-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001378969.1(KCND3):c.1942A>G(p.Asn648Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,614,046 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N648S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001378969.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCND3 | NM_001378969.1 | c.1942A>G | p.Asn648Asp | missense_variant | 8/8 | ENST00000302127.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCND3 | ENST00000302127.5 | c.1942A>G | p.Asn648Asp | missense_variant | 8/8 | 5 | NM_001378969.1 | P3 | |
KCND3 | ENST00000315987.6 | c.1942A>G | p.Asn648Asp | missense_variant | 8/8 | 1 | P3 | ||
KCND3 | ENST00000369697.5 | c.1885A>G | p.Asn629Asp | missense_variant | 6/6 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251168Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135784
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727248
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74336
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 03, 2021 | The p.N648D variant (also known as c.1942A>G), located in coding exon 7 of the KCND3 gene, results from an A to G substitution at nucleotide position 1942. The asparagine at codon 648 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at