chr3-128625917-G-A

Variant names:

• chr3-128625917-G-A
• rs761651988
• NM_002950.4:c.1232C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002950.4(RPN1):​c.1232C>T​(p.Ala411Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A411D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RPN1 NM_002950.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.34
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1232C>T	p.Ala411Val	missense	Exon 7 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.1232C>T	p.Ala411Val	missense	Exon 7 of 10	ENSP00000296255.3	P04843
	RPN1	ENST00000874295.1		c.1232C>T	p.Ala411Val	missense	Exon 7 of 10	ENSP00000544354.1
	RPN1	ENST00000916581.1		c.1232C>T	p.Ala411Val	missense	Exon 7 of 10	ENSP00000586640.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Benign	22
DANN	Benign	0.81
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.062
Eigen_PC	Benign	0.075
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.4	L
PhyloP100		9.3
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.72	N
REVEL	Benign	0.22
Sift	Benign	0.72	T
Sift4G	Benign	1.0	T
Polyphen		0.13	B
Vest4		0.77
MutPred		0.45		Gain of sheet (P = 0.0344)
MVP		0.53
MPC		0.30
ClinPred		0.91	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.64
Mutation Taster		=43/57	disease causing

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

Other links and lift over

dbSNP: rs761651988; hg19: chr3-128344760;