1-201982707-G-T

Variant names:

• chr1-201982707-G-T
• rs770984111
• NM_020216.4:c.41G>T

Variant summary

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

The NM_001319183.2(RNPEP):​c.-827G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000787 in 1,398,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: RNPEP NM_001319183.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127

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=0.082791835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNPEP	NM_020216.4	c.41G>T	p.Arg14Leu	missense_variant	Exon 1 of 11	ENST00000295640.9	NP_064601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNPEP	ENST00000295640.9	c.41G>T	p.Arg14Leu	missense_variant	Exon 1 of 11	1	NM_020216.4	ENSP00000295640.4

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151426 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

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: 0.00

Gnomad OTH AF: 0.000481

GnomAD3 exomes AF: 0.0000384 AC: 2 AN: 52128 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 30028

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000885

Gnomad NFE exome AF: 0.0000613

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000561 AC: 7 AN: 1246838 Hom.: 0 Cov.: 29 AF XY: 0.00000327 AC XY: 2 AN XY: 611794

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000571

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000599

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000264 AC: 4 AN: 151426 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 73972

Gnomad4 AFR AF: 0.0000484

Gnomad4 AMR AF: 0.0000657

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000481

Bravo AF: 0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.54
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.76	N;N
REVEL	Benign	0.023
Sift	Benign	0.11	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.089	B;.
Vest4		0.14
MutPred		0.38		Loss of solvent accessibility (P = 0.0606);Loss of solvent accessibility (P = 0.0606);
MVP		0.20
MPC		0.21
ClinPred		0.046	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.070
gMVP		0.40

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: rs770984111; hg19: chr1-201951835;