rs863223400

Variant names:

• chr8-56073724-C-CT
• rs863223400
• NM_001023.4:c.147dupA

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001023.4(RPS20):​c.147dupA​(p.Val50SerfsTer23) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPS20 NM_001023.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 0.299
• Publications: 9 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]

SNORD54 (HGNC:10204): (small nucleolar RNA, C/D box 54)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.592 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001023.4. 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_001023.4	MANE Select	c.147dupA	p.Val50SerfsTer23	frameshift	Exon 3 of 4	NP_001014.1	P60866-1
	RPS20	NM_001146227.3		c.147dupA	p.Val50SerfsTer23	frameshift	Exon 3 of 6	NP_001139699.1	P60866-2
	SNORD54	NR_002437.1		n.*114dupA		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS20	ENST00000009589.8	TSL:1 MANE Select	c.147dupA	p.Val50SerfsTer23	frameshift	Exon 3 of 4	ENSP00000009589.3	P60866-1
	RPS20	ENST00000524349.5	TSL:1	c.-19dupA		5_prime_UTR	Exon 2 of 3	ENSP00000429049.1	G3XAN0
	RPS20	ENST00000519807.5	TSL:2	c.147dupA	p.Val50SerfsTer23	frameshift	Exon 3 of 6	ENSP00000429374.1	P60866-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

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
PhyloP100		0.30
Mutation Taster		=3/197	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs863223400; hg19: chr8-56986283;