2-55233475-AGGT-A

Variant summary

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

The NM_002954.6(RPS27A):c.103+60_103+62del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00784 in 1,221,246 control chromosomes in the GnomAD database, including 459 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (277 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (182 hom.)
• Consequence: RPS27A NM_002954.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.56

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 2-55233475-AGGT-A is Benign according to our data. Variant chr2-55233475-AGGT-A is described in ClinVar as [Benign]. Clinvar id is 1253611.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	UniProt
RPS27A	NM_002954.6	c.103+60_103+62del		intron_variant		ENST00000272317.11
RPS27A	NM_001135592.2	c.103+60_103+62del		intron_variant
RPS27A	NM_001177413.1	c.103+60_103+62del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS27A	ENST00000272317.11	c.103+60_103+62del		intron_variant		1	NM_002954.6	P1

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 5113 AN: 152146 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: 0.00417 AC: 4461 AN: 1068982 Hom.: 182 AF XY: 0.00352 AC XY: 1935 AN XY: 549396

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.00821

Gnomad4 ASJ exome AF: 0.000254

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000588

Gnomad4 OTH exome AF: 0.00951

GnomAD4 genome AF: 0.0336 AC: 5115 AN: 152264 Hom.: 277 Cov.: 33 AF XY: 0.0320 AC XY: 2384 AN XY: 74458

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

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Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs60340564; hg19: chr2-55460611;