Variant 15-74956218-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_017793.3(RPP25):c.366G>A(p.Pro122Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,561,710 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00094 ( 36 hom. )

Consequence

RPP25
NM_017793.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.19

Variant links:

Genes affected

RPP25 (HGNC:30361): (ribonuclease P and MRP subunit p25) Enables ribonuclease P RNA binding activity. Contributes to ribonuclease P activity. Involved in tRNA 5'-leader removal. Located in centriolar satellite and nucleoplasm. Part of multimeric ribonuclease P complex and ribonuclease MRP complex. Biomarker of autistic disorder. [provided by Alliance of Genome Resources, Apr 2022]

RPP25 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

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

BP6

Variant 15-74956218-C-T is Benign according to our data. Variant chr15-74956218-C-T is described in ClinVar as [Benign]. Clinvar id is 769887.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.19 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00237 (361/152370) while in subpopulation AMR AF= 0.0208 (319/15308). AF 95% confidence interval is 0.019. There are 7 homozygotes in gnomad4. There are 205 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPP25	NM_017793.3 linkuse as main transcript	c.366G>A	p.Pro122Pro	synonymous_variant	1/1	ENST00000322177.6	NP_060263.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPP25	ENST00000322177.6 linkuse as main transcript	c.366G>A	p.Pro122Pro	synonymous_variant	1/1	6	NM_017793.3	ENSP00000317691.6		Q9BUL9

Frequencies

GnomAD3 genomes

AF:

0.00234

AC:

357

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0206

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00578

AC:

1025

AN:

177302

Hom.:

AF XY:

0.00437

AC XY:

424

AN XY:

97018

show subpopulations

Gnomad AFR exome

AF:

0.000387

Gnomad AMR exome

AF:

0.0410

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000388

Gnomad OTH exome

AF:

0.00469

GnomAD4 exome

AF:

0.000935

AC:

1318

AN:

1409340

Hom.:

Cov.:

AF XY:

0.000802

AC XY:

558

AN XY:

695714

show subpopulations

Gnomad4 AFR exome

AF:

0.000310

Gnomad4 AMR exome

AF:

0.0347

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000265

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000193

Gnomad4 OTH exome

AF:

0.000808

GnomAD4 genome

AF:

0.00237

AC:

361

AN:

152370

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

205

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.000793

Gnomad4 AMR

AF:

0.0208

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000814

Hom.:

Bravo

AF:

0.00402

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.5

DANN

Benign

0.86

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