Genetic Variant RNPEP:p.Thr184Thr (chr1-201989008-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020216.4(RNPEP):c.552G>A(p.Thr184Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,614,064 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 106 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 79 hom. )

Consequence

RNPEP
NM_020216.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.66

Publications

2 publications found

Variant links:

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]

RNPEP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 1-201989008-G-A is Benign according to our data. Variant chr1-201989008-G-A is described in ClinVar as Benign. ClinVar VariationId is 767743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RNPEP	NM_020216.4	MANE Select	c.552G>A	p.Thr184Thr	synonymous	Exon 2 of 11	NP_064601.3
RNPEP	NM_001319182.2		c.159G>A	p.Thr53Thr	synonymous	Exon 2 of 11	NP_001306111.1
RNPEP	NM_001319183.2		c.-316G>A		5_prime_UTR	Exon 2 of 10	NP_001306112.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNPEP	ENST00000295640.9	TSL:1 MANE Select	c.552G>A	p.Thr184Thr	synonymous	Exon 2 of 11	ENSP00000295640.4	Q9H4A4
RNPEP	ENST00000471105.5	TSL:1	n.264G>A		non_coding_transcript_exon	Exon 2 of 10
RNPEP	ENST00000967255.1		c.552G>A	p.Thr184Thr	synonymous	Exon 2 of 11	ENSP00000637314.1

Frequencies

GnomAD3 genomes

AF:

0.0199

AC:

3026

AN:

152122

Hom.:

105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0690

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00786

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0144

GnomAD2 exomes

AF:

0.00524

AC:

1317

AN:

251370

AF XY:

0.00371

show subpopulations

Gnomad AFR exome

AF:

0.0709

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00207

AC:

3019

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

1259

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.0709

AC:

2374

AN:

33472

American (AMR)

AF:

0.00398

AC:

178

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00161

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000174

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00330

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000863

AC:

AN:

1111992

Other (OTH)

AF:

0.00488

AC:

295

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

145

291

436

582

727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0199

AC:

3030

AN:

152240

Hom.:

106

Cov.:

AF XY:

0.0192

AC XY:

1426

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0689

AC:

2860

AN:

41520

American (AMR)

AF:

0.00785

AC:

120

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68028

Other (OTH)

AF:

0.0142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

144

288

431

575

719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00765

Hom.:

Bravo

AF:

0.0229

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.6

(source)

DANN

Benign

0.55

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over