rs1281876553

Variant names:

• chr1-201983063-G-T
• rs1281876553
• NM_020216.4:c.397G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-201983063-G-T
• chr1-201983063-G-A
• chr1-201983063-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020216.4(RNPEP):​c.397G>T​(p.Ala133Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000801 in 1,373,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000080 (0 hom.)
• Consequence: RNPEP NM_020216.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.397
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0611988).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020216.4. 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
	RNPEP	NM_020216.4	MANE Select	c.397G>T	p.Ala133Ser	missense	Exon 1 of 11	NP_064601.3
	RNPEP	NM_001319183.2		c.-471G>T		5_prime_UTR	Exon 1 of 10	NP_001306112.1
	RNPEP	NM_001319184.2		c.-325G>T		5_prime_UTR	Exon 1 of 10	NP_001306113.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNPEP	ENST00000295640.9	TSL:1 MANE Select	c.397G>T	p.Ala133Ser	missense	Exon 1 of 11	ENSP00000295640.4	Q9H4A4
	RNPEP	ENST00000471105.5	TSL:1	n.109G>T		non_coding_transcript_exon	Exon 1 of 10
	RNPEP	ENST00000967255.1		c.397G>T	p.Ala133Ser	missense	Exon 1 of 11	ENSP00000637314.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000326 AC: 4 AN: 122714 AF XY: 0.0000431

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000914

Gnomad NFE exome AF: 0.0000407

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000801 AC: 11 AN: 1373030 Hom.: 0 Cov.: 29 AF XY: 0.00000883 AC XY: 6 AN XY: 679280

African (AFR) AF: 0.00 AC: 0 AN: 28578

American (AMR) AF: 0.00 AC: 0 AN: 32818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23796

East Asian (EAS) AF: 0.00 AC: 0 AN: 32560

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 76786

European-Finnish (FIN) AF: 0.0000232 AC: 1 AN: 43112

Middle Eastern (MID) AF: 0.000214 AC: 1 AN: 4664

European-Non Finnish (NFE) AF: 0.00000652 AC: 7 AN: 1073918

Other (OTH) AF: 0.0000176 AC: 1 AN: 56798

GnomAD4 genome Cov.: 32

Alfa AF: 0.000153 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

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	0.073
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.55	N
PhyloP100		0.40
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.016
Sift	Benign	0.11	T
Sift4G	Benign	0.47	T
Polyphen		0.0010	B
Vest4		0.039
MutPred		0.39		Gain of phosphorylation at A133 (P = 0.0837)
MVP		0.22
MPC		0.14
ClinPred		0.062	T
GERP RS		0.45
PromoterAI		-0.0033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.1
Varity_R		0.062
gMVP		0.31
Mutation Taster		=95/5	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: rs1281876553; hg19: chr1-201952191;