NM_020216.4:c.290G>C

Variant names:

• chr1-201982956-G-C
• rs549263851
• NM_020216.4:c.290G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020216.4(RNPEP):​c.290G>C​(p.Arg97Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. R97L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNPEP NM_020216.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916

Genes affected

RNPEP (HGNC:10078): (arginyl aminopeptidase) Predicted to enable metalloaminopeptidase activity. Predicted to be involved in proteolysis. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07742727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNPEP	NM_020216.4	c.290G>C	p.Arg97Pro	missense_variant	Exon 1 of 11	ENST00000295640.9	NP_064601.3
RNPEP	NM_001319183.2	c.-578G>C		5_prime_UTR_variant	Exon 1 of 10		NP_001306112.1
RNPEP	NM_001319184.2	c.-432G>C		5_prime_UTR_variant	Exon 1 of 10		NP_001306113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNPEP	ENST00000295640.9	c.290G>C	p.Arg97Pro	missense_variant	Exon 1 of 11	1	NM_020216.4	ENSP00000295640.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.46
DANN	Benign	0.82
DEOGEN2	Benign	0.040	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.16	N;N
REVEL	Benign	0.0
Sift	Benign	0.28	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.0	B;.
Vest4		0.11
MutPred		0.41		Gain of glycosylation at R97 (P = 0.0213);Gain of glycosylation at R97 (P = 0.0213);
MVP		0.17
MPC		0.23
ClinPred		0.058	T
GERP RS		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs549263851; hg19: chr1-201952084;