2-55235327-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002954.6(RPS27A):c.322-101A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 1,311,332 control chromosomes in the GnomAD database, including 239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (125 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (114 hom.)
• Consequence: RPS27A NM_002954.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.44

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-55235327-A-T is Benign according to our data. Variant chr2-55235327-A-T is described in ClinVar as [Benign]. Clinvar id is 1231269.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS27A	NM_002954.6	c.322-101A>T		intron_variant		ENST00000272317.11
RPS27A	NM_001135592.2	c.322-101A>T		intron_variant
RPS27A	NM_001177413.1	c.322-101A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS27A	ENST00000272317.11	c.322-101A>T		intron_variant		1	NM_002954.6	P1
RPS27A	ENST00000404735.1	c.322-101A>T		intron_variant		1		P1
RPS27A	ENST00000402285.7	c.322-101A>T		intron_variant		3		P1
RPS27A	ENST00000495843.1	n.978-101A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3451 AN: 152232 Hom.: 124 Cov.: 32

Gnomad AFR AF: 0.0792

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00713

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: 0.000191

Gnomad OTH AF: 0.0181

GnomAD4 exome AF: 0.00248 AC: 2878 AN: 1158982 Hom.: 114 Cov.: 16 AF XY: 0.00213 AC XY: 1256 AN XY: 590944

Gnomad4 AFR exome AF: 0.0878

Gnomad4 AMR exome AF: 0.00344

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000876

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000497

Gnomad4 OTH exome AF: 0.00505

GnomAD4 genome AF: 0.0227 AC: 3464 AN: 152350 Hom.: 125 Cov.: 32 AF XY: 0.0219 AC XY: 1629 AN XY: 74508

Gnomad4 AFR AF: 0.0793

Gnomad4 AMR AF: 0.00712

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0173 Hom.: 10

Bravo AF: 0.0260

Asia WGS AF: 0.00404 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.60

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: rs72918921; hg19: chr2-55462463;