rs11156878

chr14-35266761-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (1393 hom., cov: 31)
  • Exomes 𝑓: 0.16 (18631 hom.)
• Consequence: PRORP NM_014672.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.63

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-PSMA6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 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 criteria_provided_single_submitter, 1 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	UniProt
PRORP	NM_014672.4	c.1310A>G	p.Asn437Ser	missense_variant	6/8	ENST00000534898.9
PRORP-PSMA6	NR_182666.1	n.1818A>G		non_coding_transcript_exon_variant	6/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRORP	ENST00000534898.9	c.1310A>G	p.Asn437Ser	missense_variant	6/8	1	NM_014672.4	P1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19036 AN: 152082 Hom.: 1394 Cov.: 31

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

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.: 32 AF XY: 0.155 AC XY: 112350 AN XY: 727164

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.: 31 AF XY: 0.121 AC XY: 9020 AN XY: 74424

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: criteria provided, single submitter

Submissions by phenotype

PRORP-related condition Benign:1

Benign, criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	22
Dann	Uncertain	0.99
Eigen	Benign	0.056
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.88	D
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	T
MutationTaster	Benign	0.51	P;P;P;P;P;P
PrimateAI	Benign	0.48	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	T
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

Other links and lift over

dbSNP: rs11156878; hg19: chr14-35735967; COSMIC: COSV51617748; COSMIC: COSV51617748;