Genetic Variant RPS25:n.263T>C (chr11-119018404-A-G) – 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.-120T>C 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 0.983 in 1,425,736 control chromosomes in the GnomAD database, including 689,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 74240 hom., cov: 35)

Exomes 𝑓: 0.98 ( 614949 hom. )

Consequence

RPS25
ENST00000527791.5 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.121

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:

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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=-0.8).

BP6

Variant 11-119018404-A-G is Benign according to our data. Variant chr11-119018404-A-G is described in ClinVar as [Benign]. Clinvar id is 1267945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS25	NM_001028.3 link	c.-120T>C		upstream_gene_variant		ENST00000527673.2	NP_001019.1	P62851

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS25	ENST00000527673.2 link	c.-120T>C		upstream_gene_variant		1	NM_001028.3	ENSP00000435096.1		P62851

Frequencies

GnomAD3 genomes

AF:

0.987

AC:

150295

AN:

152258

Hom.:

74181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.996

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.987

Gnomad ASJ

AF:

0.988

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

0.982

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.980

Gnomad OTH

AF:

0.985

GnomAD4 exome

AF:

0.983

AC:

1251374

AN:

1273360

Hom.:

614949

Cov.:

AF XY:

0.983

AC XY:

627235

AN XY:

637958

show subpopulations

Gnomad4 AFR exome

AF:

0.997

Gnomad4 AMR exome

AF:

0.988

Gnomad4 ASJ exome

AF:

0.985

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.998

Gnomad4 FIN exome

AF:

0.979

Gnomad4 NFE exome

AF:

0.980

Gnomad4 OTH exome

AF:

0.984

GnomAD4 genome

AF:

0.987

AC:

150413

AN:

152376

Hom.:

74240

Cov.:

AF XY:

0.988

AC XY:

73584

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.996

Gnomad4 AMR

AF:

0.987

Gnomad4 ASJ

AF:

0.988

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

0.982

Gnomad4 NFE

AF:

0.980

Gnomad4 OTH

AF:

0.985

Alfa

AF:

0.982

Hom.:

23033

Bravo

AF:

0.988

Asia WGS

AF:

0.998

AC:

3470

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

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.78

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