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GeneBe

3-128637793-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002950.4(RPN1):c.633+6C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0095 in 1,609,678 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0068 ( 8 hom., cov: 32)
Exomes 𝑓: 0.0098 ( 90 hom. )

Consequence

RPN1
NM_002950.4 splice_donor_region, intron

Scores

2
Splicing: ADA: 0.00002130
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.269
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 3-128637793-G-A is Benign according to our data. Variant chr3-128637793-G-A is described in ClinVar as [Benign]. Clinvar id is 774848.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPN1NM_002950.4 linkuse as main transcriptc.633+6C>T splice_donor_region_variant, intron_variant ENST00000296255.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPN1ENST00000296255.8 linkuse as main transcriptc.633+6C>T splice_donor_region_variant, intron_variant 1 NM_002950.4 P1
RPN1ENST00000497289.5 linkuse as main transcriptc.117+6C>T splice_donor_region_variant, intron_variant 2
RPN1ENST00000495462.5 linkuse as main transcriptn.529+6C>T splice_donor_region_variant, intron_variant, non_coding_transcript_variant 3
RPN1ENST00000479113.1 linkuse as main transcript downstream_gene_variant 4

Frequencies

GnomAD3 genomes
AF:
0.00681
AC:
1036
AN:
152172
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00133
Gnomad AMI
AF:
0.0515
Gnomad AMR
AF:
0.00255
Gnomad ASJ
AF:
0.00173
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00372
Gnomad FIN
AF:
0.0168
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0100
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.00766
AC:
1918
AN:
250436
Hom.:
12
AF XY:
0.00771
AC XY:
1043
AN XY:
135348
show subpopulations
Gnomad AFR exome
AF:
0.00166
Gnomad AMR exome
AF:
0.00324
Gnomad ASJ exome
AF:
0.00230
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00386
Gnomad FIN exome
AF:
0.0150
Gnomad NFE exome
AF:
0.0112
Gnomad OTH exome
AF:
0.00818
GnomAD4 exome
AF:
0.00979
AC:
14262
AN:
1457388
Hom.:
90
Cov.:
31
AF XY:
0.00959
AC XY:
6949
AN XY:
724472
show subpopulations
Gnomad4 AFR exome
AF:
0.00159
Gnomad4 AMR exome
AF:
0.00327
Gnomad4 ASJ exome
AF:
0.00219
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00473
Gnomad4 FIN exome
AF:
0.0147
Gnomad4 NFE exome
AF:
0.0111
Gnomad4 OTH exome
AF:
0.00760
GnomAD4 genome
AF:
0.00680
AC:
1036
AN:
152290
Hom.:
8
Cov.:
32
AF XY:
0.00698
AC XY:
520
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.00132
Gnomad4 AMR
AF:
0.00255
Gnomad4 ASJ
AF:
0.00173
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00373
Gnomad4 FIN
AF:
0.0168
Gnomad4 NFE
AF:
0.0100
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00748
Hom.:
4
Bravo
AF:
0.00577
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.00954
EpiControl
AF:
0.00984

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 01, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
4.0
DANN
Benign
0.49
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.2

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000021
dbscSNV1_RF
Benign
0.0020
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: rs150096055; hg19: chr3-128356636; API