2-55234687-T-A

Position:

• chr2-55234687-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002954.6(RPS27A):​c.190-144T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 878,656 control chromosomes in the GnomAD database, including 297,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52885 hom., cov: 32)
  • Exomes 𝑓: 0.82 (244761 hom.)
• Consequence: RPS27A NM_002954.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.372

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 2-55234687-T-A is Benign according to our data. Variant chr2-55234687-T-A is described in ClinVar as [Benign]. Clinvar id is 1292677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS27A	NM_002954.6	c.190-144T>A		intron_variant		ENST00000272317.11	NP_002945.1
RPS27A	NM_001135592.2	c.190-144T>A		intron_variant			NP_001129064.1
RPS27A	NM_001177413.1	c.190-144T>A		intron_variant			NP_001170884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS27A	ENST00000272317.11	c.190-144T>A		intron_variant		1	NM_002954.6	ENSP00000272317	P1

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126637 AN: 152100 Hom.: 52852 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.827

GnomAD4 exome AF: 0.819 AC: 595069 AN: 726438 Hom.: 244761 Cov.: 9 AF XY: 0.817 AC XY: 310609 AN XY: 380134

Gnomad4 AFR exome AF: 0.834

Gnomad4 AMR exome AF: 0.764

Gnomad4 ASJ exome AF: 0.742

Gnomad4 EAS exome AF: 0.687

Gnomad4 SAS exome AF: 0.754

Gnomad4 FIN exome AF: 0.885

Gnomad4 NFE exome AF: 0.839

Gnomad4 OTH exome AF: 0.814

GnomAD4 genome AF: 0.833 AC: 126725 AN: 152218 Hom.: 52885 Cov.: 32 AF XY: 0.831 AC XY: 61828 AN XY: 74428

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.700

Gnomad4 SAS AF: 0.729

Gnomad4 FIN AF: 0.891

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.829

Alfa AF: 0.821 Hom.: 2618

Bravo AF: 0.827

Asia WGS AF: 0.731 AC: 2543 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.6
DANN	Benign	0.58

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: rs2576722; hg19: chr2-55461823;