2-55235387-G-A

Position:

• chr2-55235387-G-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.322-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,607,012 control chromosomes in the GnomAD database, including 334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (158 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (176 hom.)
• Consequence: RPS27A NM_002954.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.16

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=-0.86).
• BP6: Variant 2-55235387-G-A is Benign according to our data. Variant chr2-55235387-G-A is described in ClinVar as [Benign]. Clinvar id is 1257434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS27A	NM_002954.6	c.322-41G>A		intron_variant		ENST00000272317.11	NP_002945.1
RPS27A	NM_001135592.2	c.322-41G>A		intron_variant			NP_001129064.1
RPS27A	NM_001177413.1	c.322-41G>A		intron_variant			NP_001170884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS27A	ENST00000272317.11	c.322-41G>A		intron_variant		1	NM_002954.6	ENSP00000272317	P1
RPS27A	ENST00000404735.1	c.322-41G>A		intron_variant		1		ENSP00000385659	P1
RPS27A	ENST00000402285.7	c.322-41G>A		intron_variant		3		ENSP00000383981	P1
RPS27A	ENST00000495843.1	n.978-41G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0248 AC: 3771 AN: 152190 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.0866

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.00633 AC: 1586 AN: 250652 Hom.: 63 AF XY: 0.00463 AC XY: 628 AN XY: 135590

Gnomad AFR exome AF: 0.0894

Gnomad AMR exome AF: 0.00335

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00267 AC: 3881 AN: 1454704 Hom.: 176 Cov.: 29 AF XY: 0.00232 AC XY: 1677 AN XY: 724110

Gnomad4 AFR exome AF: 0.0985

Gnomad4 AMR exome AF: 0.00365

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000479

Gnomad4 OTH exome AF: 0.00599

GnomAD4 genome AF: 0.0249 AC: 3797 AN: 152308 Hom.: 158 Cov.: 32 AF XY: 0.0242 AC XY: 1801 AN XY: 74482

Gnomad4 AFR AF: 0.0869

Gnomad4 AMR AF: 0.00791

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0123 Hom.: 16

Bravo AF: 0.0282

Asia WGS AF: 0.00866 AC: 31 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	-0.86
CADD	Benign	2.5
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs72918923; hg19: chr2-55462523;