3-128625538-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002950.4(RPN1):āc.1391C>Gā(p.Thr464Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_002950.4 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 |
---|---|---|---|---|---|---|---|
RPN1 | NM_002950.4 | c.1391C>G | p.Thr464Ser | missense_variant | 8/10 | ENST00000296255.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPN1 | ENST00000296255.8 | c.1391C>G | p.Thr464Ser | missense_variant | 8/10 | 1 | NM_002950.4 | P1 | |
RPN1 | ENST00000497289.5 | c.875C>G | p.Thr292Ser | missense_variant | 8/10 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250436Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135374
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461866Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727232
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 20, 2023 | The c.1391C>G (p.T464S) alteration is located in exon 8 (coding exon 8) of the RPN1 gene. This alteration results from a C to G substitution at nucleotide position 1391, causing the threonine (T) at amino acid position 464 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