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rs34781001

chr3-128620588-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_002950.4(RPN1):c.1647C>T(p.Ser549=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,612,680 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 40 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 34 hom. )

Consequence

RPN1
NM_002950.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.16
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 -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-128620588-G-A is Benign according to our data. Variant chr3-128620588-G-A is described in ClinVar as [Benign]. Clinvar id is 720033.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.16 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1951/152216) while in subpopulation AFR AF= 0.0432 (1796/41526). AF 95% confidence interval is 0.0416. There are 40 homozygotes in gnomad4. There are 903 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 40 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPN1NM_002950.4 linkuse as main transcriptc.1647C>T p.Ser549= synonymous_variant 10/10 ENST00000296255.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPN1ENST00000296255.8 linkuse as main transcriptc.1647C>T p.Ser549= synonymous_variant 10/101 NM_002950.4 P1
RPN1ENST00000497289.5 linkuse as main transcriptc.1131C>T p.Ser377= synonymous_variant 10/102

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0128
AC:
1950
AN:
152098
Hom.:
40
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0434
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00832
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.0125
GnomAD3 exomes
AF:
0.00348
AC:
862
AN:
247462
Hom.:
15
AF XY:
0.00245
AC XY:
329
AN XY:
134028
show subpopulations
Gnomad AFR exome
AF:
0.0479
Gnomad AMR exome
AF:
0.00191
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.000164
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000541
Gnomad OTH exome
AF:
0.00132
GnomAD4 exome
AF:
0.00126
AC:
1843
AN:
1460464
Hom.:
34
Cov.:
31
AF XY:
0.00107
AC XY:
775
AN XY:
726448
show subpopulations
Gnomad4 AFR exome
AF:
0.0457
Gnomad4 AMR exome
AF:
0.00231
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000209
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000441
Gnomad4 OTH exome
AF:
0.00227
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0128
AC:
1951
AN:
152216
Hom.:
40
Cov.:
32
AF XY:
0.0121
AC XY:
903
AN XY:
74408
show subpopulations
Gnomad4 AFR
AF:
0.0432
Gnomad4 AMR
AF:
0.00831
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.0123
Alfa
AF:
0.00565
Hom.:
11
Bravo
AF:
0.0153
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.0000546
EpiControl
AF:
0.00

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
-0.56
Cadd
Benign
3.7
Dann
Benign
0.65
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs34781001; hg19: chr3-128339431; API