chr2-55234273-T-C

Position:

• chr2-55234273-T-C

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.189+69T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,147,760 control chromosomes in the GnomAD database, including 1,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (906 hom., cov: 32)
  • Exomes 𝑓: 0.0078 (605 hom.)
• Consequence: RPS27A NM_002954.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.504

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 (MetaRNN=0.0018050075).
• BP6: Variant 2-55234273-T-C is Benign according to our data. Variant chr2-55234273-T-C is described in ClinVar as [Benign]. Clinvar id is 1242743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS27A	NM_002954.6	c.189+69T>C		intron_variant		ENST00000272317.11	NP_002945.1
RPS27A	NM_001135592.2	c.189+69T>C		intron_variant			NP_001129064.1
RPS27A	NM_001177413.1	c.189+69T>C		intron_variant			NP_001170884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS27A	ENST00000272317.11	c.189+69T>C		intron_variant		1	NM_002954.6	ENSP00000272317	P1

Frequencies

GnomAD3 genomes AF: 0.0608 AC: 9242 AN: 152126 Hom.: 908 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0317

Gnomad ASJ AF: 0.0211

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00168

Gnomad OTH AF: 0.0435

GnomAD4 exome AF: 0.00782 AC: 7786 AN: 995518 Hom.: 605 Cov.: 13 AF XY: 0.00681 AC XY: 3502 AN XY: 513984

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.0147

Gnomad4 ASJ exome AF: 0.0224

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000254

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00121

Gnomad4 OTH exome AF: 0.0187

GnomAD4 genome AF: 0.0607 AC: 9247 AN: 152242 Hom.: 906 Cov.: 32 AF XY: 0.0582 AC XY: 4334 AN XY: 74426

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.0316

Gnomad4 ASJ AF: 0.0211

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00166

Gnomad4 OTH AF: 0.0431

Alfa AF: 0.0388 Hom.: 86

Bravo AF: 0.0711

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.000519 AC: 2

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 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.85
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0018	T
MutationTaster	Benign	0.92	P;P;P
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs74478570; hg19: chr2-55461409;