3-128625917-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002950.4(RPN1):​c.1232C>G​(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

Scores

4
11
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.34
Variant links:
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]

Genome browser will be placed here

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

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPN1NM_002950.4 linkc.1232C>G p.Ala411Gly missense_variant Exon 7 of 10 ENST00000296255.8 NP_002941.1 P04843

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPN1ENST00000296255.8 linkc.1232C>G p.Ala411Gly missense_variant Exon 7 of 10 1 NM_002950.4 ENSP00000296255.3 P04843
RPN1ENST00000497289.5 linkc.716C>G p.Ala239Gly missense_variant Exon 7 of 10 2 ENSP00000417529.1 B7Z4L4
RPN1ENST00000490166.1 linkn.*57C>G downstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
250948
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135644
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461410
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727038
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.40
T;T
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.97
D;D
M_CAP
Benign
0.033
D
MetaRNN
Uncertain
0.68
D;D
MetaSVM
Uncertain
-0.14
T
MutationAssessor
Uncertain
2.5
M;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-2.9
D;D
REVEL
Uncertain
0.64
Sift
Uncertain
0.018
D;D
Sift4G
Uncertain
0.021
D;D
Polyphen
0.98
D;.
Vest4
0.78
MutPred
0.62
Gain of catalytic residue at P407 (P = 0.0721);.;
MVP
0.52
MPC
0.31
ClinPred
0.98
D
GERP RS
4.6
Varity_R
0.73
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs761651988; hg19: chr3-128344760; API