rs60340564

Variant names:

• chr2-55233475-AGGT-A
• rs60340564
• NM_002954.6:c.103+60_103+62delGTG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002954.6(RPS27A):​c.103+60_103+62delGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00784 in 1,221,246 control chromosomes in the GnomAD database, including 459 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (277 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (182 hom.)
• Consequence: RPS27A NM_002954.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.56
• Publications: 0 publications found

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 -10 ACMG points.

• BP6: Variant 2-55233475-AGGT-A is Benign according to our data. Variant chr2-55233475-AGGT-A is described in ClinVar as Benign. ClinVar VariationId is 1253611.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002954.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS27A	NM_002954.6	MANE Select	c.103+60_103+62delGTG		intron	N/A	NP_002945.1	B2RDW1
	RPS27A	NM_001135592.2		c.103+60_103+62delGTG		intron	N/A	NP_001129064.1	B2RDW1
	RPS27A	NM_001177413.1		c.103+60_103+62delGTG		intron	N/A	NP_001170884.1	B2RDW1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS27A	ENST00000272317.11	TSL:1 MANE Select	c.103+60_103+62delGTG		intron	N/A	ENSP00000272317.6	P62979
	RPS27A	ENST00000404735.1	TSL:1	c.103+60_103+62delGTG		intron	N/A	ENSP00000385659.1	P62979
	RPS27A	ENST00000859841.1		c.103+60_103+62delGTG		intron	N/A	ENSP00000529900.1

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 5113 AN: 152146 Hom.: 277 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0185

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.0297

GnomAD4 exome AF: 0.00417 AC: 4461 AN: 1068982 Hom.: 182 AF XY: 0.00352 AC XY: 1935 AN XY: 549396

African (AFR) AF: 0.122 AC: 3161 AN: 25946

American (AMR) AF: 0.00821 AC: 354 AN: 43142

Ashkenazi Jewish (ASJ) AF: 0.000254 AC: 6 AN: 23662

East Asian (EAS) AF: 0.00 AC: 0 AN: 37676

South Asian (SAS) AF: 0.000116 AC: 9 AN: 77412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52846

Middle Eastern (MID) AF: 0.0101 AC: 36 AN: 3562

European-Non Finnish (NFE) AF: 0.000588 AC: 445 AN: 757426

Other (OTH) AF: 0.00951 AC: 450 AN: 47310

GnomAD4 genome AF: 0.0336 AC: 5115 AN: 152264 Hom.: 277 Cov.: 33 AF XY: 0.0320 AC XY: 2384 AN XY: 74458

African (AFR) AF: 0.113 AC: 4703 AN: 41514

American (AMR) AF: 0.0184 AC: 282 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000941 AC: 64 AN: 68034

Other (OTH) AF: 0.0294 AC: 62 AN: 2108

Alfa AF: 0.0270 Hom.: 0

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs60340564; hg19: chr2-55460611;