Variant 3-128637793-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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

Splicing: ADA: 0.00002130

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

RPN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 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_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPN1	NM_002950.4 linkuse as main transcript	c.633+6C>T		splice_donor_region_variant, intron_variant		ENST00000296255.8	NP_002941.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
RPN1	ENST00000296255.8 linkuse as main transcript	c.633+6C>T	splice_donor_region_variant, intron_variant	1	NM_002950.4	ENSP00000296255	P1
RPN1	ENST00000497289.5 linkuse as main transcript	c.117+6C>T	splice_donor_region_variant, intron_variant	2		ENSP00000417529
RPN1	ENST00000495462.5 linkuse as main transcript	n.529+6C>T	splice_donor_region_variant, intron_variant, non_coding_transcript_variant	3
RPN1	ENST00000479113.1 linkuse as main transcript		downstream_gene_variant	4

Frequencies

GnomAD3 genomes

AF:

0.00681

AC:

1036

AN:

152172

Hom.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.00577

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00954

EpiControl

AF:

0.00984

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 01, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over