3-128650748-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_002950.4(RPN1):c.53C>T(p.Ala18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000619 in 1,551,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002950.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPN1 | NM_002950.4 | c.53C>T | p.Ala18Val | missense_variant | 1/10 | ENST00000296255.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPN1 | ENST00000296255.8 | c.53C>T | p.Ala18Val | missense_variant | 1/10 | 1 | NM_002950.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000342 AC: 52AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000660 AC: 10AN: 151568Hom.: 0 AF XY: 0.0000616 AC XY: 5AN XY: 81204
GnomAD4 exome AF: 0.0000314 AC: 44AN: 1399356Hom.: 0 Cov.: 32 AF XY: 0.0000174 AC XY: 12AN XY: 690370
GnomAD4 genome ? AF: 0.000341 AC: 52AN: 152346Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19AN XY: 74490
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2022 | The c.53C>T (p.A18V) alteration is located in exon 1 (coding exon 1) of the RPN1 gene. This alteration results from a C to T substitution at nucleotide position 53, causing the alanine (A) at amino acid position 18 to be replaced by a valine (V). 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