8-56069824-A-G

Position:

• chr8-56069824-A-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.343T>C​(p.Ser115Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00578 in 1,495,880 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (79 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (99 hom.)
• Consequence: RPS20 NM_001146227.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.347

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 (MetaRNN=0.0018868148).
• BP6: Variant 8-56069824-A-G is Benign according to our data. Variant chr8-56069824-A-G is described in ClinVar as [Benign]. Clinvar id is 1232012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS20	NM_001146227.3	c.343T>C	p.Ser115Pro	missense_variant	5/6		NP_001139699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS20	ENST00000519807.5	c.343T>C	p.Ser115Pro	missense_variant	5/6	2		ENSP00000429374
RPS20	ENST00000618656.2	c.325T>C	p.Ser109Pro	missense_variant	4/5	3		ENSP00000478703
RPS20	ENST00000676461.1	c.*2547+719T>C		intron_variant, NMD_transcript_variant				ENSP00000504670

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2955 AN: 152118 Hom.: 77 Cov.: 32

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.00785 AC: 1209 AN: 153948 Hom.: 28 AF XY: 0.00747 AC XY: 610 AN XY: 81706

Gnomad AFR exome AF: 0.0699

Gnomad AMR exome AF: 0.00652

Gnomad ASJ exome AF: 0.00330

Gnomad EAS exome AF: 0.0151

Gnomad SAS exome AF: 0.00606

Gnomad FIN exome AF: 0.0000656

Gnomad NFE exome AF: 0.00233

Gnomad OTH exome AF: 0.00600

GnomAD4 exome AF: 0.00423 AC: 5681 AN: 1343644 Hom.: 99 Cov.: 22 AF XY: 0.00416 AC XY: 2769 AN XY: 665856

Gnomad4 AFR exome AF: 0.0640

Gnomad4 AMR exome AF: 0.00688

Gnomad4 ASJ exome AF: 0.00375

Gnomad4 EAS exome AF: 0.0226

Gnomad4 SAS exome AF: 0.00573

Gnomad4 FIN exome AF: 0.000102

Gnomad4 NFE exome AF: 0.00161

Gnomad4 OTH exome AF: 0.00740

GnomAD4 genome AF: 0.0195 AC: 2964 AN: 152236 Hom.: 79 Cov.: 32 AF XY: 0.0192 AC XY: 1429 AN XY: 74442

Gnomad4 AFR AF: 0.0604

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.0179

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00190

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0118 Hom.: 16

Bravo AF: 0.0221

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0665 AC: 92

ESP6500EA AF: 0.00157 AC: 5

ExAC AF: 0.0109 AC: 240

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 30, 2020	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -

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_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.3
DANN	Benign	0.75
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.58	.;T
MetaRNN	Benign	0.0019	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.49	N;.
REVEL	Benign	0.037
Sift	Benign	0.14	T;.
Sift4G	Benign	0.14	T;T
Vest4		0.17
MPC		1.4
ClinPred		0.0030	T
GERP RS		0.81
gMVP		0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs79444047; hg19: chr8-56982383;