2-55233469-A-T

Variant names:

• chr2-55233469-A-T
• rs6737227
• NM_002954.6:c.103+52A>T

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.103+52A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 1,341,404 control chromosomes in the GnomAD database, including 387,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44256 hom., cov: 32)
  • Exomes 𝑓: 0.76 (343273 hom.)
• Consequence: RPS27A NM_002954.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.63

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=-0.88).
• BP6: Variant 2-55233469-A-T is Benign according to our data. Variant chr2-55233469-A-T is described in ClinVar as [Benign]. Clinvar id is 1238560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS27A	NM_002954.6	c.103+52A>T		intron_variant	Intron 3 of 5	ENST00000272317.11	NP_002945.1
RPS27A	NM_001135592.2	c.103+52A>T		intron_variant	Intron 3 of 5		NP_001129064.1
RPS27A	NM_001177413.1	c.103+52A>T		intron_variant	Intron 2 of 4		NP_001170884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS27A	ENST00000272317.11	c.103+52A>T		intron_variant	Intron 3 of 5	1	NM_002954.6	ENSP00000272317.6

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115713 AN: 151954 Hom.: 44220 Cov.: 32

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.760

GnomAD2 exomes AF: 0.741 AC: 178080 AN: 240220 AF XY: 0.740

Gnomad AFR exome AF: 0.764

Gnomad AMR exome AF: 0.714

Gnomad ASJ exome AF: 0.666

Gnomad EAS exome AF: 0.642

Gnomad FIN exome AF: 0.841

Gnomad NFE exome AF: 0.767

Gnomad OTH exome AF: 0.741

GnomAD4 exome AF: 0.758 AC: 902075 AN: 1189332 Hom.: 343273 Cov.: 16 AF XY: 0.757 AC XY: 457708 AN XY: 604954

Gnomad4 AFR exome AF: 0.761 AC: 21245 AN: 27930

Gnomad4 AMR exome AF: 0.717 AC: 31249 AN: 43580

Gnomad4 ASJ exome AF: 0.663 AC: 16157 AN: 24372

Gnomad4 EAS exome AF: 0.618 AC: 23584 AN: 38168

Gnomad4 SAS exome AF: 0.683 AC: 54678 AN: 80088

Gnomad4 FIN exome AF: 0.840 AC: 44552 AN: 53018

Gnomad4 NFE exome AF: 0.773 AC: 669895 AN: 867124

Gnomad4 Remaining exome AF: 0.745 AC: 38167 AN: 51252

GnomAD4 genome AF: 0.761 AC: 115800 AN: 152072 Hom.: 44256 Cov.: 32 AF XY: 0.761 AC XY: 56552 AN XY: 74322

Gnomad4 AFR AF: 0.765 AC: 0.764719 AN: 0.764719

Gnomad4 AMR AF: 0.741 AC: 0.741364 AN: 0.741364

Gnomad4 ASJ AF: 0.655 AC: 0.654755 AN: 0.654755

Gnomad4 EAS AF: 0.627 AC: 0.627417 AN: 0.627417

Gnomad4 SAS AF: 0.658 AC: 0.657949 AN: 0.657949

Gnomad4 FIN AF: 0.844 AC: 0.844423 AN: 0.844423

Gnomad4 NFE AF: 0.773 AC: 0.773173 AN: 0.773173

Gnomad4 OTH AF: 0.763 AC: 0.762559 AN: 0.762559

Alfa AF: 0.724 Hom.: 4498

Bravo AF: 0.756

Asia WGS AF: 0.667 AC: 2320 AN: 3478

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 14, 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	-0.88
CADD	Benign	0.30
DANN	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs6737227; hg19: chr2-55460605;