8-56069456-A-G

Position:

• chr8-56069456-A-G

Variant summary

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

The NM_001146227.3(RPS20):​c.*35+247T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,780 control chromosomes in the GnomAD database, including 5,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (5994 hom., cov: 31)
• Consequence: RPS20 NM_001146227.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.502

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 8-56069456-A-G is Benign according to our data. Variant chr8-56069456-A-G is described in ClinVar as [Benign]. Clinvar id is 1223975.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS20	NM_001146227.3	c.*35+247T>C		intron_variant			NP_001139699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS20	ENST00000519807.5	c.*35+247T>C		intron_variant		2		ENSP00000429374
RPS20	ENST00000618656.2	c.*35+247T>C		intron_variant		3		ENSP00000478703
RPS20	ENST00000676461.1	c.*2547+1087T>C		intron_variant, NMD_transcript_variant				ENSP00000504670

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41093 AN: 151662 Hom.: 5990 Cov.: 31

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.288

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.271 AC: 41131 AN: 151780 Hom.: 5994 Cov.: 31 AF XY: 0.263 AC XY: 19488 AN XY: 74170

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.0240

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.285

Alfa AF: 0.252 Hom.: 660

Bravo AF: 0.282

Asia WGS AF: 0.0970 AC: 338 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

Jun 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.27
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2976050; hg19: chr8-56982015;