Genetic Variant RPS25:n.-384C>T (chr11-119018668-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000527791.5(RPS25):n.-384C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,088,050 control chromosomes in the GnomAD database, including 53,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 14113 hom., cov: 33)

Exomes 𝑓: 0.27 ( 39554 hom. )

Consequence

RPS25
ENST00000527791.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.22

Variant links:

Genes affected

RPS25 (HGNC:10413): (ribosomal protein S25) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S25E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPS25 links:

TRAPPC4 (HGNC:19943): (trafficking protein particle complex subunit 4) Involved in autophagy and endoplasmic reticulum to Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

TRAPPC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 11-119018668-G-A is Benign according to our data. Variant chr11-119018668-G-A is described in ClinVar as [Benign]. Clinvar id is 1240845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC4	NM_016146.6 link	c.-128G>A		upstream_gene_variant		ENST00000533632.6	NP_057230.1	Q9Y296-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC4	ENST00000533632.6 link	c.-128G>A		upstream_gene_variant		1	NM_016146.6	ENSP00000436005.1		Q9Y296-1

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58414

AN:

151732

Hom.:

14064

Cov.:

show subpopulations

Gnomad AFR

AF:

0.693

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.347

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.341

GnomAD4 exome

AF:

0.272

AC:

254646

AN:

936200

Hom.:

39554

Cov.:

AF XY:

0.275

AC XY:

130833

AN XY:

476148

show subpopulations

Gnomad4 AFR exome

AF:

0.703

Gnomad4 AMR exome

AF:

0.209

Gnomad4 ASJ exome

AF:

0.209

Gnomad4 EAS exome

AF:

0.155

Gnomad4 SAS exome

AF:

0.357

Gnomad4 FIN exome

AF:

0.307

Gnomad4 NFE exome

AF:

0.257

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.385

AC:

58517

AN:

151850

Hom.:

14113

Cov.:

AF XY:

0.384

AC XY:

28479

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.693

Gnomad4 AMR

AF:

0.279

Gnomad4 ASJ

AF:

0.199

Gnomad4 EAS

AF:

0.149

Gnomad4 SAS

AF:

0.373

Gnomad4 FIN

AF:

0.324

Gnomad4 NFE

AF:

0.264

Gnomad4 OTH

AF:

0.343

Alfa

AF:

0.305

Hom.:

1693

Bravo

AF:

0.394

Asia WGS

AF:

0.298

AC:

1039

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.75

DANN

Benign

0.82

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