rs56696262

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001029.5(RPS26):c.327T>A(p.Arg109Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,612,816 control chromosomes in the GnomAD database, including 2,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 1477 hom., cov: 31)

Exomes 𝑓: 0.0078 ( 1345 hom. )

Consequence

RPS26
NM_001029.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.32

Variant links:

Genes affected

RPS26 (HGNC:10414): (ribosomal protein S26) This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S26E family of ribosomal proteins. Mutations in this gene are found in Diamond-Blackfan anemia 10. There are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Aug 2017]

RPS26 links:

RPS26 (HGNC:):

RPS26 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 12-56044133-T-A is Benign according to our data. Variant chr12-56044133-T-A is described in ClinVar as [Benign]. Clinvar id is 309860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.32 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS26	NM_001029.5 linkuse as main transcript	c.327T>A	p.Arg109Arg	synonymous_variant	4/4	ENST00000646449.2	NP_001020.2	P62854A0A024RB14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RPS26	ENST00000646449.2 linkuse as main transcript	c.327T>A	p.Arg109Arg	synonymous_variant	4/4		NM_001029.5	ENSP00000496643.1	P62854
RPS26	ENST00000356464.10 linkuse as main transcript	c.327T>A	p.Arg109Arg	synonymous_variant	5/5	1		ENSP00000348849.5	P62854
RPS26	ENST00000552361.1 linkuse as main transcript	c.327T>A	p.Arg109Arg	synonymous_variant	5/5	5		ENSP00000450339.1	P62854
RPS26	ENST00000548590.1 linkuse as main transcript	n.1114T>A		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.0757

AC:

11483

AN:

151750

Hom.:

1467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0260

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000780

Gnomad OTH

AF:

0.0422

GnomAD3 exomes

AF:

0.0199

AC:

5013

AN:

251476

Hom.:

598

AF XY:

0.0144

AC XY:

1959

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.272

Gnomad AMR exome

AF:

0.0116

Gnomad ASJ exome

AF:

0.00536

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000721

Gnomad OTH exome

AF:

0.00798

GnomAD4 exome

AF:

0.00781

AC:

11409

AN:

1460948

Hom.:

1345

Cov.:

AF XY:

0.00668

AC XY:

4852

AN XY:

726888

show subpopulations

Gnomad4 AFR exome

AF:

0.278

Gnomad4 AMR exome

AF:

0.0134

Gnomad4 ASJ exome

AF:

0.00539

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000267

Gnomad4 OTH exome

AF:

0.0169

GnomAD4 genome

AF:

0.0759

AC:

11525

AN:

151868

Hom.:

1477

Cov.:

AF XY:

0.0728

AC XY:

5407

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.265

Gnomad4 AMR

AF:

0.0260

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000780

Gnomad4 OTH

AF:

0.0417

Alfa

AF:

0.00854

Hom.:

Bravo

AF:

0.0864

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.00130

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Diamond-Blackfan anemia 10

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 16, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Diamond-Blackfan anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 10, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.7

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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