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3-128637856-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_002950.4(RPN1):c.576G>A(p.Thr192=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00072 in 1,613,960 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00040 ( 5 hom. )

Consequence

RPN1
NM_002950.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.436
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 -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
Variant 3-128637856-C-T is Benign according to our data. Variant chr3-128637856-C-T is described in ClinVar as [Benign]. Clinvar id is 709402.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.436 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPN1NM_002950.4 linkuse as main transcriptc.576G>A p.Thr192= synonymous_variant 3/10 ENST00000296255.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPN1ENST00000296255.8 linkuse as main transcriptc.576G>A p.Thr192= synonymous_variant 3/101 NM_002950.4 P1
RPN1ENST00000497289.5 linkuse as main transcriptc.60G>A p.Thr20= synonymous_variant 3/102
RPN1ENST00000479113.1 linkuse as main transcriptn.522G>A non_coding_transcript_exon_variant 2/24
RPN1ENST00000495462.5 linkuse as main transcriptn.472G>A non_coding_transcript_exon_variant 3/43

Frequencies

GnomAD3 genomes
AF:
0.00380
AC:
578
AN:
152150
Hom.:
5
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0133
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000978
AC:
246
AN:
251474
Hom.:
3
AF XY:
0.000699
AC XY:
95
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.0138
Gnomad AMR exome
AF:
0.000434
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000397
AC:
580
AN:
1461692
Hom.:
5
Cov.:
31
AF XY:
0.000352
AC XY:
256
AN XY:
727158
show subpopulations
Gnomad4 AFR exome
AF:
0.0142
Gnomad4 AMR exome
AF:
0.000559
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.000861
GnomAD4 genome
AF:
0.00382
AC:
582
AN:
152268
Hom.:
5
Cov.:
32
AF XY:
0.00361
AC XY:
269
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.0133
Gnomad4 AMR
AF:
0.00131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00200
Hom.:
1
Bravo
AF:
0.00451
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 testingInvitaeApr 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.31
CADD
Benign
0.13
DANN
Benign
0.71
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs111781915; hg19: chr3-128356699; API