2-55234855-A-C

Variant names:

• chr2-55234855-A-C
• rs2230613
• NM_002954.6:c.214A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002954.6(RPS27A):​c.214A>C​(p.Arg72Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00284 in 1,612,484 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (57 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (72 hom.)
• Consequence: RPS27A NM_002954.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.05

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 2-55234855-A-C is Benign according to our data. Variant chr2-55234855-A-C is described in ClinVar as [Benign]. Clinvar id is 1244836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS27A	NM_002954.6	c.214A>C	p.Arg72Arg	synonymous_variant	Exon 5 of 6	ENST00000272317.11	NP_002945.1
RPS27A	NM_001135592.2	c.214A>C	p.Arg72Arg	synonymous_variant	Exon 5 of 6		NP_001129064.1
RPS27A	NM_001177413.1	c.214A>C	p.Arg72Arg	synonymous_variant	Exon 4 of 5		NP_001170884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS27A	ENST00000272317.11	c.214A>C	p.Arg72Arg	synonymous_variant	Exon 5 of 6	1	NM_002954.6	ENSP00000272317.6

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2209 AN: 152148 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00368 AC: 924 AN: 251082 AF XY: 0.00261

Gnomad AFR exome AF: 0.0505

Gnomad AMR exome AF: 0.00237

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00161 AC: 2352 AN: 1460218 Hom.: 72 Cov.: 31 AF XY: 0.00139 AC XY: 1013 AN XY: 726432

Gnomad4 AFR exome AF: 0.0588 AC: 1967 AN: 33434

Gnomad4 AMR exome AF: 0.00250 AC: 112 AN: 44716

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26132

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39680

Gnomad4 SAS exome AF: 0.0000580 AC: 5 AN: 86184

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53256

Gnomad4 NFE exome AF: 0.0000333 AC: 37 AN: 1111942

Gnomad4 Remaining exome AF: 0.00363 AC: 219 AN: 60258

GnomAD4 genome AF: 0.0146 AC: 2222 AN: 152266 Hom.: 57 Cov.: 32 AF XY: 0.0138 AC XY: 1024 AN XY: 74454

Gnomad4 AFR AF: 0.0510 AC: 0.0510062 AN: 0.0510062

Gnomad4 AMR AF: 0.00425 AC: 0.00424781 AN: 0.00424781

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000622 AC: 0.000622148 AN: 0.000622148

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000118 AC: 0.000117595 AN: 0.000117595

Gnomad4 OTH AF: 0.0118 AC: 0.0118483 AN: 0.0118483

Alfa AF: 0.0109 Hom.: 13

Bravo AF: 0.0170

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2230613; hg19: chr2-55461991;