NM_020216.4:c.1060G>A

Variant names:

• chr1-201997524-G-A
• rs200764787
• NM_020216.4:c.1060G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020216.4(RNPEP):​c.1060G>A​(p.Ala354Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,613,836 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00018 (1 hom.)
• Consequence: RNPEP NM_020216.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.36
• Publications: 3 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]

ELF3-AS1 (HGNC:40211): (ELF3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.14988992).

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.1060G>A	p.Ala354Thr	missense	Exon 5 of 11	NP_064601.3
	RNPEP	NM_001319182.2		c.667G>A	p.Ala223Thr	missense	Exon 5 of 11	NP_001306111.1
	RNPEP	NM_001319183.2		c.190G>A	p.Ala64Thr	missense	Exon 4 of 10	NP_001306112.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNPEP	ENST00000295640.9	TSL:1 MANE Select	c.1060G>A	p.Ala354Thr	missense	Exon 5 of 11	ENSP00000295640.4	Q9H4A4
	RNPEP	ENST00000471105.5	TSL:1	n.769G>A		non_coding_transcript_exon	Exon 4 of 10
	RNPEP	ENST00000967255.1		c.1057G>A	p.Ala353Thr	missense	Exon 5 of 11	ENSP00000637314.1

Frequencies

GnomAD3 genomes AF: 0.000335 AC: 51 AN: 152104 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000255 AC: 64 AN: 251446 AF XY: 0.000199

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.000281

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000175 AC: 256 AN: 1461732 Hom.: 1 Cov.: 31 AF XY: 0.000183 AC XY: 133 AN XY: 727142

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00129 AC: 69 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000156 AC: 173 AN: 1111862

Other (OTH) AF: 0.000132 AC: 8 AN: 60394

GnomAD4 genome AF: 0.000335 AC: 51 AN: 152104 Hom.: 0 Cov.: 31 AF XY: 0.000269 AC XY: 20 AN XY: 74290

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68018

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000248 Hom.: 1

Bravo AF: 0.000106

ExAC AF: 0.000321 AC: 39

EpiCase AF: 0.000218

EpiControl AF: 0.000296

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	Uncertain	0.52
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		9.4
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.35
Sift	Benign	0.050	D
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.88
MVP		0.50
MPC		0.64
ClinPred		0.15	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.56
Mutation Taster		=42/58	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: rs200764787; hg19: chr1-201966652; COSMIC: COSV55241650; COSMIC: COSV55241650;