3-128622303-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002950.4(RPN1):āc.1502A>Gā(p.Asn501Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,614,252 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 (ā ).
Frequency
Genomes: š 0.00024 ( 0 hom., cov: 33)
Exomes š: 0.000040 ( 0 hom. )
Consequence
RPN1
NM_002950.4 missense
NM_002950.4 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 7.57
Genes affected
RPN1 (HGNC:10381): (ribophorin I) This gene encodes a type I integral membrane protein found only in the rough endoplasmic reticulum. The encoded protein is part of an N-oligosaccharyl transferase complex that links high mannose oligosaccharides to asparagine residues found in the Asn-X-Ser/Thr consensus motif of nascent polypeptide chains. This protein forms part of the regulatory subunit of the 26S proteasome and may mediate binding of ubiquitin-like domains to this proteasome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.28632122).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPN1 | NM_002950.4 | c.1502A>G | p.Asn501Ser | missense_variant | 9/10 | ENST00000296255.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPN1 | ENST00000296255.8 | c.1502A>G | p.Asn501Ser | missense_variant | 9/10 | 1 | NM_002950.4 | P1 | |
RPN1 | ENST00000497289.5 | c.986A>G | p.Asn329Ser | missense_variant | 9/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000243 AC: 37AN: 152240Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251488Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135914
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GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461894Hom.: 0 Cov.: 33 AF XY: 0.0000454 AC XY: 33AN XY: 727248
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GnomAD4 genome ? AF: 0.000243 AC: 37AN: 152358Hom.: 0 Cov.: 33 AF XY: 0.000228 AC XY: 17AN XY: 74504
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 06, 2023 | The c.1502A>G (p.N501S) alteration is located in exon 9 (coding exon 9) of the RPN1 gene. This alteration results from a A to G substitution at nucleotide position 1502, causing the asparagine (N) at amino acid position 501 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at