chr12-56044133-T-A

Variant names:

• chr12-56044133-T-A
• rs56696262
• NM_001029.5:c.327T>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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 (★★). Synonymous variant affecting the same amino acid position (i.e. R109R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.076 (1477 hom., cov: 31)
  • Exomes 𝑓: 0.0078 (1345 hom.)
• Consequence: RPS26 NM_001029.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.32
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 10

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS26	NM_001029.5	MANE Select	c.327T>A	p.Arg109Arg	synonymous	Exon 4 of 4	NP_001020.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS26	ENST00000646449.2	MANE Select	c.327T>A	p.Arg109Arg	synonymous	Exon 4 of 4	ENSP00000496643.1	P62854
	RPS26	ENST00000356464.10	TSL:1	c.327T>A	p.Arg109Arg	synonymous	Exon 5 of 5	ENSP00000348849.5	P62854
	RPS26	ENST00000552361.1	TSL:5	c.327T>A	p.Arg109Arg	synonymous	Exon 5 of 5	ENSP00000450339.1	P62854

Frequencies

GnomAD3 genomes AF: 0.0757 AC: 11483 AN: 151750 Hom.: 1467 Cov.: 31

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

GnomAD2 exomes AF: 0.0199 AC: 5013 AN: 251476 AF XY: 0.0144

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 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.: 30 AF XY: 0.00668 AC XY: 4852 AN XY: 726888

African (AFR) AF: 0.278 AC: 9254 AN: 33330

American (AMR) AF: 0.0134 AC: 599 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00539 AC: 141 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000522 AC: 45 AN: 86248

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53418

Middle Eastern (MID) AF: 0.00850 AC: 49 AN: 5766

European-Non Finnish (NFE) AF: 0.000267 AC: 297 AN: 1111264

Other (OTH) AF: 0.0169 AC: 1022 AN: 60366

GnomAD4 genome AF: 0.0759 AC: 11525 AN: 151868 Hom.: 1477 Cov.: 31 AF XY: 0.0728 AC XY: 5407 AN XY: 74236

African (AFR) AF: 0.265 AC: 10952 AN: 41298

American (AMR) AF: 0.0260 AC: 396 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000624 AC: 3 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000780 AC: 53 AN: 67970

Other (OTH) AF: 0.0417 AC: 88 AN: 2108

Alfa AF: 0.00854 Hom.: 34

Bravo AF: 0.0864

Asia WGS AF: 0.0140 AC: 49 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.00130

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Diamond-Blackfan anemia 10 (3)
-	-	1	Diamond-Blackfan anemia (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.7
DANN	Benign	0.78
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs56696262; hg19: chr12-56437917;