Variant chr14-35123473-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014672.4(PRORP):c.228G>A(p.Lys76Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,614,150 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 14 hom. )

Consequence

PRORP
NM_014672.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.09

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 14-35123473-G-A is Benign according to our data. Variant chr14-35123473-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2644164.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.09 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRORP	NM_014672.4 linkuse as main transcript	c.228G>A	p.Lys76Lys	synonymous_variant	2/8	ENST00000534898.9	NP_055487.2	O15091-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRORP	ENST00000534898.9 linkuse as main transcript	c.228G>A	p.Lys76Lys	synonymous_variant	2/8	1	NM_014672.4	ENSP00000440915.2		O15091-1
ENSG00000258790	ENST00000557565.1 linkuse as main transcript	n.228G>A		non_coding_transcript_exon_variant	2/15	2		ENSP00000454657.1

Frequencies

GnomAD3 genomes

AF:

0.00269

AC:

409

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00650

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00435

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00321

AC:

808

AN:

251406

Hom.:

AF XY:

0.00308

AC XY:

419

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00764

Gnomad NFE exome

AF:

0.00503

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00420

AC:

6135

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00411

AC XY:

2990

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.000783

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00779

Gnomad4 NFE exome

AF:

0.00495

Gnomad4 OTH exome

AF:

0.00237

GnomAD4 genome

AF:

0.00269

AC:

409

AN:

152320

Hom.:

Cov.:

AF XY:

0.00260

AC XY:

194

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00650

Gnomad4 NFE

AF:

0.00435

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00351

Hom.:

Bravo

AF:

0.00244

EpiCase

AF:

0.00311

EpiControl

AF:

0.00362

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

PRORP: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.1

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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