Variant chr14-35266761-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 links:

ENSG00000258790 (HGNC:):

ENSG00000258790 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
PRORP	NM_014672.4 link	c.1310A>G	p.Asn437Ser	missense_variant	6/8	ENST00000534898.9	NP_055487.2	O15091-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRORP	ENST00000534898.9 link	c.1310A>G	p.Asn437Ser	missense_variant	6/8	1	NM_014672.4	ENSP00000440915.2		O15091-1
ENSG00000258790	ENST00000557565.1 link	n.1310A>G		non_coding_transcript_exon_variant	6/15	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

GnomAD3 exomes

AF:

0.136

AC:

34124

AN:

251364

Hom.:

2515

AF XY:

0.138

AC XY:

18756

AN XY:

135842

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 SAS exome

AF:

0.107

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

Gnomad4 AFR exome

AF:

0.0586

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.245

Gnomad4 EAS exome

AF:

0.0448

Gnomad4 SAS exome

AF:

0.107

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.167

Gnomad4 OTH exome

AF:

0.158

GnomAD4 genome

AF:

0.125

AC:

19040

AN:

152200

Hom.:

1393

Cov.:

AF XY:

0.121

AC XY:

9020

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0596

Gnomad4 AMR

AF:

0.141

Gnomad4 ASJ

AF:

0.230

Gnomad4 EAS

AF:

0.0609

Gnomad4 SAS

AF:

0.111

Gnomad4 FIN

AF:

0.0899

Gnomad4 NFE

AF:

0.165

Gnomad4 OTH

AF:

0.159

Alfa

AF:

0.162

Hom.:

5494

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 22, 2019

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

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0068

.;.;.;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

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.3

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

REVEL

Benign

0.039

Sift

Benign

0.26

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

Sift4G

Benign

0.49

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

Polyphen

0.13

.;.;B;B;B;.;.

Vest4

0.10

MPC

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over