rs142889882

Variant names:

• chr3-128622303-T-C
• rs142889882
• NM_002950.4:c.1502A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_002950.4(RPN1):​c.1502A>G​(p.Asn501Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,614,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: RPN1 NM_002950.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 2 publications found

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]

ENSG00000306468 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28632122).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002950.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPN1	NM_002950.4	MANE Select	c.1502A>G	p.Asn501Ser	missense	Exon 9 of 10	NP_002941.1	P04843

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPN1	ENST00000296255.8	TSL:1 MANE Select	c.1502A>G	p.Asn501Ser	missense	Exon 9 of 10	ENSP00000296255.3	P04843
	RPN1	ENST00000874295.1		c.1544A>G	p.Asn515Ser	missense	Exon 9 of 10	ENSP00000544354.1
	RPN1	ENST00000916581.1		c.1499A>G	p.Asn500Ser	missense	Exon 9 of 10	ENSP00000586640.1

Frequencies

GnomAD3 genomes AF: 0.000243 AC: 37 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000875 AC: 22 AN: 251488 AF XY: 0.0000883

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000397 AC: 58 AN: 1461894 Hom.: 0 Cov.: 33 AF XY: 0.0000454 AC XY: 33 AN XY: 727248

African (AFR) AF: 0.000568 AC: 19 AN: 33480

American (AMR) AF: 0.000291 AC: 13 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1112012

Other (OTH) AF: 0.000116 AC: 7 AN: 60396

GnomAD4 genome AF: 0.000243 AC: 37 AN: 152358 Hom.: 0 Cov.: 33 AF XY: 0.000228 AC XY: 17 AN XY: 74504

African (AFR) AF: 0.000794 AC: 33 AN: 41586

American (AMR) AF: 0.000196 AC: 3 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000137 Hom.: 0

Bravo AF: 0.000332

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000906 AC: 11

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T
Eigen	Benign	0.054
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.88	N
REVEL	Uncertain	0.41
Sift	Benign	0.52	T
Sift4G	Benign	0.73	T
Polyphen		0.23	B
Vest4		0.76
MVP		0.30
MPC		0.23
ClinPred		0.084	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.29
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs142889882; hg19: chr3-128341146;