8-56072854-C-T

Variant names:

• chr8-56072854-C-T
• rs116472667
• NM_001146227.3:c.333+263G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001146227.3(RPS20):​c.333+263G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,068,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: RPS20 NM_001146227.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754
• 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):

• familial colorectal cancer

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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.333+263G>A		intron	N/A	NP_001139699.1	P60866-2
	RPS20	NM_001023.4	MANE Select	c.*236G>A		downstream_gene	N/A	NP_001014.1	P60866-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS20	ENST00000519807.5	TSL:2	c.333+263G>A		intron	N/A	ENSP00000429374.1	P60866-2
	RPS20	ENST00000618656.2	TSL:3	c.315+263G>A		intron	N/A	ENSP00000478703.2	A0A7P0S5H5
	RPS20	ENST00000676461.1		n.*236G>A		non_coding_transcript_exon	Exon 4 of 5	ENSP00000504670.1	P60866-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000374 AC: 4 AN: 1068404 Hom.: 0 Cov.: 27 AF XY: 0.00000591 AC XY: 3 AN XY: 507586

African (AFR) AF: 0.00 AC: 0 AN: 24378

American (AMR) AF: 0.00 AC: 0 AN: 11680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12664

East Asian (EAS) AF: 0.00 AC: 0 AN: 21540

South Asian (SAS) AF: 0.00 AC: 0 AN: 37646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2600

European-Non Finnish (NFE) AF: 0.00000443 AC: 4 AN: 903734

Other (OTH) AF: 0.00 AC: 0 AN: 41500

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.68
PhyloP100		-0.75

Splicing

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

Other links and lift over

dbSNP: rs116472667; hg19: chr8-56985413;