rs1281876553

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_020216.4(RNPEP):​c.397G>A​(p.Ala133Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,373,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. A133S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: RNPEP NM_020216.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397

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=0.07609442).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNPEP	NM_020216.4	c.397G>A	p.Ala133Thr	missense_variant	Exon 1 of 11	ENST00000295640.9	NP_064601.3
RNPEP	NM_001319183.2	c.-471G>A		5_prime_UTR_variant	Exon 1 of 10		NP_001306112.1
RNPEP	NM_001319184.2	c.-325G>A		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.397G>A	p.Ala133Thr	missense_variant	Exon 1 of 11	1	NM_020216.4	ENSP00000295640.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1373026 Hom.: 0 Cov.: 29 AF XY: 0.00000147 AC XY: 1 AN XY: 679276

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000420

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.20	N;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.92	N;N
REVEL	Benign	0.043
Sift	Benign	0.057	T;D
Sift4G	Benign	0.31	T;T
Polyphen		0.020	B;.
Vest4		0.056
MutPred		0.47		Gain of phosphorylation at A133 (P = 0.0771);Gain of phosphorylation at A133 (P = 0.0771);
MVP		0.22
MPC		0.15
ClinPred		0.17	T
GERP RS		0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.1
Varity_R		0.060
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-201952191;