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GeneBe

3-128620588-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
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
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
Synonymous conserved (PhyloP=-2.16 with no splicing effect.
BS1
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. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 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
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
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