dbSNP rs11156878: PRORP:p.Asn437Ser (chr14-35266761-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_014672.4(PRORP):c.1310A>G(p.Asn437Ser) variant causes a missense change. The variant allele was found at a frequency of 0.152 in 1,613,910 control chromosomes in the GnomAD database, including 20,024 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.13 ( 1393 hom., cov: 31)

Exomes 𝑓: 0.16 ( 18631 hom. )

Consequence

PRORP
NM_014672.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.63

Publications

35 publications found

Variant links:

Genes affected

PRORP (HGNC:19958): (protein only RNase P catalytic subunit) Enables ribonuclease P activity. Involved in mitochondrial tRNA 5'-end processing. Located in mitochondrion and nucleoplasm. Part of mitochondrial ribonuclease P complex. [provided by Alliance of Genome Resources, Apr 2022]

PRORP Gene-Disease associations (from GenCC):

combined oxidative phosphorylation deficiency 54
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

PRORP links:

ENSG00000258790 (HGNC:):

ENSG00000258790 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016128123).

BP6

Variant 14-35266761-A-G is Benign according to our data. Variant chr14-35266761-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060555.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRORP	NM_014672.4 link	c.1310A>G	p.Asn437Ser	missense_variant	Exon 6 of 8	ENST00000534898.9	NP_055487.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRORP	ENST00000534898.9 link	c.1310A>G	p.Asn437Ser	missense_variant	Exon 6 of 8	1	NM_014672.4	ENSP00000440915.2
ENSG00000258790	ENST00000557565.1 link	n.1310A>G		non_coding_transcript_exon_variant	Exon 6 of 15	2		ENSP00000454657.1

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

19036

AN:

152082

Hom.:

1394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0598

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.0609

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0899

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.160

GnomAD2 exomes

AF:

0.136

AC:

34124

AN:

251364

AF XY:

0.138

show subpopulations

Gnomad AFR exome

AF:

0.0572

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.242

Gnomad EAS exome

AF:

0.0633

Gnomad FIN exome

AF:

0.0969

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.154

GnomAD4 exome

AF:

0.155

AC:

226894

AN:

1461710

Hom.:

18631

Cov.:

AF XY:

0.155

AC XY:

112350

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.0586

AC:

1963

AN:

33478

American (AMR)

AF:

0.125

AC:

5601

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

6405

AN:

26126

East Asian (EAS)

AF:

0.0448

AC:

1778

AN:

39696

South Asian (SAS)

AF:

0.107

AC:

9252

AN:

86250

European-Finnish (FIN)

AF:

0.104

AC:

5541

AN:

53416

Middle Eastern (MID)

AF:

0.216

AC:

1246

AN:

5768

European-Non Finnish (NFE)

AF:

0.167

AC:

185566

AN:

1111882

Other (OTH)

AF:

0.158

AC:

9542

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

9477

18954

28432

37909

47386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6478

12956

19434

25912

32390

<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:

0.125

AC:

19040

AN:

152200

Hom.:

1393

Cov.:

AF XY:

0.121

AC XY:

9020

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0596

AC:

2473

AN:

41524

American (AMR)

AF:

0.141

AC:

2151

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

798

AN:

3470

East Asian (EAS)

AF:

0.0609

AC:

316

AN:

5190

South Asian (SAS)

AF:

0.111

AC:

535

AN:

4826

European-Finnish (FIN)

AF:

0.0899

AC:

952

AN:

10588

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.165

AC:

11217

AN:

68010

Other (OTH)

AF:

0.159

AC:

336

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

837

1675

2512

3350

4187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<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:

0.156

Hom.:

7803

Bravo

AF:

0.127

TwinsUK

AF:

0.177

AC:

655

ALSPAC

AF:

0.163

AC:

629

ESP6500AA

AF:

0.0608

AC:

268

ESP6500EA

AF:

0.168

AC:

1446

ExAC

AF:

0.135

AC:

16434

Asia WGS

AF:

0.0830

AC:

287

AN:

3478

EpiCase

AF:

0.175

EpiControl

AF:

0.177

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRORP-related disorder

Benign:1

Oct 22, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0

.;.;.;T;.;.;T

Eigen

Benign

0.056

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.81

T;T;.;T;T;.;T

MetaRNN

Benign

0.0016

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;.;.;.;.;.;.

PhyloP100

5.6

PrimateAI

Benign

0.48

PROVEAN

Benign

0.0

.;.;.;N;.;.;N

REVEL

Benign

0.0

Sift

Pathogenic

0.0

.;.;.;T;.;.;T

Sift4G

Benign

0.49

T;T;T;T;T;T;T

Vest4

0.10

ClinPred

0.020

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.65

gMVP

0.12

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over