chr8-56073094-G-A

Variant names:

• chr8-56073094-G-A
• rs762595301
• NM_001023.4:c.356C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001023.4(RPS20):​c.356C>T​(p.Ala119Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A119G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPS20 NM_001023.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.81
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3629735).

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.356C>T	p.Ala119Val	missense	Exon 4 of 4	NP_001014.1	P60866-1
	RPS20	NM_001146227.3		c.333+23C>T		intron	N/A	NP_001139699.1	P60866-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS20	ENST00000009589.8	TSL:1 MANE Select	c.356C>T	p.Ala119Val	missense	Exon 4 of 4	ENSP00000009589.3	P60866-1
	RPS20	ENST00000524349.5	TSL:1	c.191C>T	p.Ala64Val	missense	Exon 3 of 3	ENSP00000429049.1	G3XAN0
	RPS20	ENST00000521262.5	TSL:2	c.356C>T	p.Ala119Val	missense	Exon 4 of 4	ENSP00000427788.1	P60866-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000428 AC: 1 AN: 233638 AF XY: 0.00000784

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.94e-7 AC: 1 AN: 1441134 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 716944

African (AFR) AF: 0.00 AC: 0 AN: 33216

American (AMR) AF: 0.00 AC: 0 AN: 43636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25986

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4196

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109704

Other (OTH) AF: 0.00 AC: 0 AN: 59950

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.053
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.6	L
PhyloP100		9.8
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.28
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.032	B
Vest4		0.64
MutPred		0.27		Gain of sheet (P = 0.0477)
MVP		0.46
ClinPred		0.68	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
Mutation Taster		=9/91	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: rs762595301; hg19: chr8-56985653;