Genetic Variant RPS27A:c.103+198C>T (chr2-55233615-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_002954.6(RPS27A):c.103+198C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 601,414 control chromosomes in the GnomAD database, including 165,310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43060 hom., cov: 31)

Exomes 𝑓: 0.74 ( 122250 hom. )

Consequence

RPS27A
NM_002954.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.978

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=-0.88).

BP6

Variant 2-55233615-C-T is Benign according to our data. Variant chr2-55233615-C-T is described in ClinVar as [Benign]. Clinvar id is 1246341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RPS27A	NM_002954.6 link	c.103+198C>T	intron_variant	Intron 3 of 5	ENST00000272317.11	NP_002945.1	P62979B2RDW1
RPS27A	NM_001135592.2 link	c.103+198C>T	intron_variant	Intron 3 of 5		NP_001129064.1	P62979B2RDW1
RPS27A	NM_001177413.1 link	c.103+198C>T	intron_variant	Intron 2 of 4		NP_001170884.1	P62979B2RDW1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS27A	ENST00000272317.11 link	c.103+198C>T		intron_variant	Intron 3 of 5	1	NM_002954.6	ENSP00000272317.6		P62979

Frequencies

GnomAD3 genomes

AF:

0.751

AC:

114129

AN:

151964

Hom.:

43025

Cov.:

show subpopulations

Gnomad AFR

AF:

0.762

Gnomad AMI

AF:

0.822

Gnomad AMR

AF:

0.726

Gnomad ASJ

AF:

0.635

Gnomad EAS

AF:

0.640

Gnomad SAS

AF:

0.654

Gnomad FIN

AF:

0.842

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.757

Gnomad OTH

AF:

0.747

GnomAD4 exome

AF:

0.735

AC:

330299

AN:

449332

Hom.:

122250

Cov.:

AF XY:

0.732

AC XY:

175562

AN XY:

239852

show subpopulations

Gnomad4 AFR exome

AF:

0.753

Gnomad4 AMR exome

AF:

0.709

Gnomad4 ASJ exome

AF:

0.644

Gnomad4 EAS exome

AF:

0.619

Gnomad4 SAS exome

AF:

0.676

Gnomad4 FIN exome

AF:

0.835

Gnomad4 NFE exome

AF:

0.754

Gnomad4 OTH exome

AF:

0.730

GnomAD4 genome

AF:

0.751

AC:

114214

AN:

152082

Hom.:

43060

Cov.:

AF XY:

0.750

AC XY:

55783

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.761

Gnomad4 AMR

AF:

0.726

Gnomad4 ASJ

AF:

0.635

Gnomad4 EAS

AF:

0.641

Gnomad4 SAS

AF:

0.653

Gnomad4 FIN

AF:

0.842

Gnomad4 NFE

AF:

0.757

Gnomad4 OTH

AF:

0.750

Alfa

AF:

0.746

Hom.:

67700

Bravo

AF:

0.745

Asia WGS

AF:

0.668

AC:

2325

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

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

0.28

DANN

Benign

0.72

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