19-14446428-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002741.5(PKN1):c.477C>A(p.Asp159Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002741.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PKN1 | NM_002741.5 | c.477C>A | p.Asp159Glu | missense_variant, splice_region_variant | Exon 4 of 22 | ENST00000242783.11 | NP_002732.3 | |
PKN1 | NM_213560.3 | c.495C>A | p.Asp165Glu | missense_variant, splice_region_variant | Exon 4 of 22 | NP_998725.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000525 AC: 8AN: 152244Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248634Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134944
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461396Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726970
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74384
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.495C>A (p.D165E) alteration is located in exon 4 (coding exon 4) of the PKN1 gene. This alteration results from a C to A substitution at nucleotide position 495, causing the aspartic acid (D) at amino acid position 165 to be replaced by a glutamic acid (E). 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