2-55233470-CCTGT-C

Position:

• chr2-55233470-CCTGT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000272317.11(RPS27A):​c.103+54_103+57del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00772 in 1,251,506 control chromosomes in the GnomAD database, including 461 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (277 hom., cov: 33)
  • Exomes 𝑓: 0.0041 (184 hom.)
• Consequence: RPS27A ENST00000272317.11 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0400

Genes affected

RPS27A (HGNC:10417): (ribosomal protein S27a) Ubiquitin, a highly conserved protein that has a major role in targeting cellular proteins for degradation by the 26S proteosome, is synthesized as a precursor protein consisting of either polyubiquitin chains or a single ubiquitin fused to an unrelated protein. This gene encodes a fusion protein consisting of ubiquitin at the N terminus and ribosomal protein S27a at the C terminus. When expressed in yeast, the protein is post-translationally processed, generating free ubiquitin monomer and ribosomal protein S27a. Ribosomal protein S27a is a component of the 40S subunit of the ribosome and belongs to the S27AE family of ribosomal proteins. It contains C4-type zinc finger domains and is located in the cytoplasm. Pseudogenes derived from this gene are present in the genome. As with ribosomal protein S27a, ribosomal protein L40 is also synthesized as a fusion protein with ubiquitin; similarly, ribosomal protein S30 is synthesized as a fusion protein with the ubiquitin-like protein fubi. Multiple alternatively spliced transcript variants that encode the same proteins have been identified.[provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-55233470-CCTGT-C is Benign according to our data. Variant chr2-55233470-CCTGT-C is described in ClinVar as [Benign]. Clinvar id is 1228462.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS27A	NM_002954.6	c.103+54_103+57del		intron_variant		ENST00000272317.11	NP_002945.1
RPS27A	NM_001135592.2	c.103+54_103+57del		intron_variant			NP_001129064.1
RPS27A	NM_001177413.1	c.103+54_103+57del		intron_variant			NP_001170884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS27A	ENST00000272317.11	c.103+54_103+57del		intron_variant		1	NM_002954.6	ENSP00000272317	P1

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 5114 AN: 152116 Hom.: 277 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0185

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.0297

GnomAD4 exome AF: 0.00414 AC: 4550 AN: 1099272 Hom.: 184 AF XY: 0.00351 AC XY: 1974 AN XY: 563176

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.00815

Gnomad4 ASJ exome AF: 0.000293

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000115

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000591

Gnomad4 OTH exome AF: 0.00944

GnomAD4 genome AF: 0.0336 AC: 5116 AN: 152234 Hom.: 277 Cov.: 33 AF XY: 0.0320 AC XY: 2382 AN XY: 74426

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0184

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000941

Gnomad4 OTH AF: 0.0294

Alfa AF: 0.0270 Hom.: 0

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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

Other links and lift over

dbSNP: rs58567381; hg19: chr2-55460606;