3-128625917-G-C
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002950.4(RPN1):āc.1232C>Gā(p.Ala411Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,410 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
RPN1
NM_002950.4 missense
NM_002950.4 missense
Scores
4
11
4
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 9.34
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RPN1 | ENST00000296255.8 | c.1232C>G | p.Ala411Gly | missense_variant | Exon 7 of 10 | 1 | NM_002950.4 | ENSP00000296255.3 | ||
RPN1 | ENST00000497289.5 | c.716C>G | p.Ala239Gly | missense_variant | Exon 7 of 10 | 2 | ENSP00000417529.1 | |||
RPN1 | ENST00000490166.1 | n.*57C>G | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 250948Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135644
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461410Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727038
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GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Gain of catalytic residue at P407 (P = 0.0721);.;
MVP
MPC
ClinPred
D
GERP RS
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