8-56072854-C-G

Position:

• chr8-56072854-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001146227.3(RPS20):​c.333+263G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00571 in 1,220,546 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (80 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (73 hom.)
• Consequence: RPS20 NM_001146227.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.754

Genes affected

RPS20 (HGNC:10405): (ribosomal protein S20) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S10P family of ribosomal proteins. It is located in the cytoplasm. This gene is co-transcribed with the small nucleolar RNA gene U54, which is located in its second intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Two transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 8-56072854-C-G is Benign according to our data. Variant chr8-56072854-C-G is described in ClinVar as [Benign]. Clinvar id is 1278075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS20	NM_001146227.3	c.333+263G>C		intron_variant			NP_001139699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS20	ENST00000519807.5	c.333+263G>C		intron_variant		2		ENSP00000429374
RPS20	ENST00000618656.2	c.315+263G>C		intron_variant		3		ENSP00000478703
RPS20	ENST00000676461.1	c.*236G>C		3_prime_UTR_variant, NMD_transcript_variant	4/5			ENSP00000504670

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2953 AN: 152064 Hom.: 78 Cov.: 32

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.00375 AC: 4004 AN: 1068364 Hom.: 73 Cov.: 27 AF XY: 0.00373 AC XY: 1895 AN XY: 507570

Gnomad4 AFR exome AF: 0.0640

Gnomad4 AMR exome AF: 0.00634

Gnomad4 ASJ exome AF: 0.00355

Gnomad4 EAS exome AF: 0.0201

Gnomad4 SAS exome AF: 0.00547

Gnomad4 FIN exome AF: 0.000158

Gnomad4 NFE exome AF: 0.00153

Gnomad4 OTH exome AF: 0.00655

GnomAD4 genome AF: 0.0195 AC: 2962 AN: 152182 Hom.: 80 Cov.: 32 AF XY: 0.0192 AC XY: 1432 AN XY: 74398

Gnomad4 AFR AF: 0.0603

Gnomad4 AMR AF: 0.0100

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.0181

Gnomad4 SAS AF: 0.00621

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.00191

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0127 Hom.: 4

Bravo AF: 0.0222

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Jun 15, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs116472667; hg19: chr8-56985413;