Variant 2-55233917-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002954.6(RPS27A):c.104-202A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 625,510 control chromosomes in the GnomAD database, including 6,320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1186 hom., cov: 32)

Exomes 𝑓: 0.14 ( 5134 hom. )

Consequence

RPS27A
NM_002954.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.411

Variant links:

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]

RPS27A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 2-55233917-A-G is Benign according to our data. Variant chr2-55233917-A-G is described in ClinVar as [Benign]. Clinvar id is 1292680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
RPS27A	NM_002954.6 linkuse as main transcript	c.104-202A>G	intron_variant	ENST00000272317.11	NP_002945.1
RPS27A	NM_001135592.2 linkuse as main transcript	c.104-202A>G	intron_variant		NP_001129064.1
RPS27A	NM_001177413.1 linkuse as main transcript	c.104-202A>G	intron_variant		NP_001170884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS27A	ENST00000272317.11 linkuse as main transcript	c.104-202A>G		intron_variant		1	NM_002954.6	ENSP00000272317	P1

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16580

AN:

152114

Hom.:

1188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0310

Gnomad AMI

AF:

0.0692

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.0867

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.110

GnomAD4 exome

AF:

0.137

AC:

64949

AN:

473276

Hom.:

5134

Cov.:

AF XY:

0.136

AC XY:

34182

AN XY:

251628

show subpopulations

Gnomad4 AFR exome

AF:

0.0317

Gnomad4 AMR exome

AF:

0.210

Gnomad4 ASJ exome

AF:

0.138

Gnomad4 EAS exome

AF:

0.266

Gnomad4 SAS exome

AF:

0.123

Gnomad4 FIN exome

AF:

0.0881

Gnomad4 NFE exome

AF:

0.131

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.109

AC:

16562

AN:

152234

Hom.:

1186

Cov.:

AF XY:

0.111

AC XY:

8235

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0310

Gnomad4 AMR

AF:

0.173

Gnomad4 ASJ

AF:

0.142

Gnomad4 EAS

AF:

0.255

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.0867

Gnomad4 NFE

AF:

0.131

Gnomad4 OTH

AF:

0.108

Alfa

AF:

0.112

Hom.:

133

Bravo

AF:

0.113

Asia WGS

AF:

0.176

AC:

613

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.5

DANN

Benign

0.22

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over