8-56069703-C-T

Variant names:

• chr8-56069703-C-T
• rs150975205
• NM_001146227.3:c.*35G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 4P and 16B. PP3_Strong BP6_Very_Strong BA1

The NM_001146227.3(RPS20):​c.*35G>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00508 in 1,546,176 control chromosomes in the GnomAD database, including 762 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (105 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (657 hom.)
• Consequence: RPS20 NM_001146227.3 splice_region
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0470
• Publications: 0 publications found

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]

RPS20 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia

  Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, Orphanet, Ambry Genetics
• familial colorectal cancer

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• familial colorectal cancer type X

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• Lynch syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 8-56069703-C-T is Benign according to our data. Variant chr8-56069703-C-T is described in ClinVar as Benign. ClinVar VariationId is 1279207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146227.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS20	NM_001146227.3		c.*35G>A		splice_region	Exon 5 of 6	NP_001139699.1	P60866-2
	RPS20	NM_001146227.3		c.*35G>A		3_prime_UTR	Exon 5 of 6	NP_001139699.1	P60866-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS20	ENST00000519807.5	TSL:2	c.*35G>A		splice_region	Exon 5 of 6	ENSP00000429374.1	P60866-2
	RPS20	ENST00000618656.2	TSL:3	c.*35G>A		splice_region	Exon 4 of 5	ENSP00000478703.2	A0A7P0S5H5
	RPS20	ENST00000519807.5	TSL:2	c.*35G>A		3_prime_UTR	Exon 5 of 6	ENSP00000429374.1	P60866-2

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1538 AN: 152150 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.00195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0930

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.0284 AC: 4369 AN: 153994 AF XY: 0.0214

Gnomad AFR exome AF: 0.00114

Gnomad AMR exome AF: 0.174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000838

Gnomad OTH exome AF: 0.0171

GnomAD4 exome AF: 0.00451 AC: 6291 AN: 1393908 Hom.: 657 Cov.: 29 AF XY: 0.00380 AC XY: 2614 AN XY: 687874

African (AFR) AF: 0.000953 AC: 30 AN: 31474

American (AMR) AF: 0.167 AC: 5947 AN: 35688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25142

East Asian (EAS) AF: 0.00 AC: 0 AN: 35702

South Asian (SAS) AF: 0.00 AC: 0 AN: 79120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.0000456 AC: 49 AN: 1073990

Other (OTH) AF: 0.00458 AC: 265 AN: 57822

GnomAD4 genome AF: 0.0102 AC: 1559 AN: 152268 Hom.: 105 Cov.: 32 AF XY: 0.0111 AC XY: 824 AN XY: 74452

African (AFR) AF: 0.00195 AC: 81 AN: 41564

American (AMR) AF: 0.0943 AC: 1440 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68020

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.00590 Hom.: 98

Bravo AF: 0.0193

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.7
DANN	Benign	0.66
PhyloP100		-0.047
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.97

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

Other links and lift over

dbSNP: rs150975205; hg19: chr8-56982262;