8-56441672-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001135690.3(PENK):c.404G>A(p.Arg135Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001135690.3 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PENK | NM_001135690.3 | c.404G>A | p.Arg135Gln | missense_variant | Exon 4 of 4 | ENST00000451791.7 | NP_001129162.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00 AC: 1AN: 152078Hom.: 0 Cov.: 32 FAILED QC
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251496Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135922
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461860Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7AN XY: 727232
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 1AN: 152078Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74284
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.404G>A (p.R135Q) alteration is located in exon 2 (coding exon 2) of the PENK gene. This alteration results from a G to A substitution at nucleotide position 404, causing the arginine (R) at amino acid position 135 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