NM_001023.4:c.104-90T>C

Variant names:

• chr8-56073858-A-G
• rs17814456
• NM_001023.4:c.104-90T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001023.4(RPS20):​c.104-90T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,271,834 control chromosomes in the GnomAD database, including 25,884 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2448 hom., cov: 32)
  • Exomes 𝑓: 0.19 (23436 hom.)
• Consequence: RPS20 NM_001023.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.31
• Publications: 11 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 8-56073858-A-G is Benign according to our data. Variant chr8-56073858-A-G is described in ClinVar as Benign. ClinVar VariationId is 1259849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

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.104-90T>C		intron	N/A	NP_001014.1	P60866-1
	RPS20	NM_001146227.3		c.104-90T>C		intron	N/A	NP_001139699.1	P60866-2
	SNORD54	NR_002437.1		n.44T>C		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS20	ENST00000009589.8	TSL:1 MANE Select	c.104-90T>C		intron	N/A	ENSP00000009589.3	P60866-1
	RPS20	ENST00000524349.5	TSL:1	c.-62-90T>C		intron	N/A	ENSP00000429049.1	G3XAN0
	RPS20	ENST00000519807.5	TSL:2	c.104-90T>C		intron	N/A	ENSP00000429374.1	P60866-2

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23640 AN: 152080 Hom.: 2448 Cov.: 32

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0823

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.187

GnomAD2 exomes AF: 0.165 AC: 41028 AN: 248794 AF XY: 0.169

Gnomad AFR exome AF: 0.0402

Gnomad AMR exome AF: 0.122

Gnomad ASJ exome AF: 0.311

Gnomad EAS exome AF: 0.000327

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.212

GnomAD4 exome AF: 0.194 AC: 216955 AN: 1119636 Hom.: 23436 Cov.: 15 AF XY: 0.193 AC XY: 110419 AN XY: 573028

African (AFR) AF: 0.0416 AC: 1115 AN: 26784

American (AMR) AF: 0.129 AC: 5703 AN: 44338

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 7581 AN: 24000

East Asian (EAS) AF: 0.000341 AC: 13 AN: 38104

South Asian (SAS) AF: 0.0872 AC: 6939 AN: 79556

European-Finnish (FIN) AF: 0.166 AC: 8644 AN: 51938

Middle Eastern (MID) AF: 0.260 AC: 1331 AN: 5126

European-Non Finnish (NFE) AF: 0.220 AC: 176078 AN: 800602

Other (OTH) AF: 0.194 AC: 9551 AN: 49188

GnomAD4 genome AF: 0.155 AC: 23638 AN: 152198 Hom.: 2448 Cov.: 32 AF XY: 0.150 AC XY: 11142 AN XY: 74406

African (AFR) AF: 0.0433 AC: 1800 AN: 41552

American (AMR) AF: 0.175 AC: 2669 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1082 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.0824 AC: 397 AN: 4820

European-Finnish (FIN) AF: 0.161 AC: 1702 AN: 10594

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15132 AN: 67986

Other (OTH) AF: 0.185 AC: 390 AN: 2110

Alfa AF: 0.170 Hom.: 922

Bravo AF: 0.155

Asia WGS AF: 0.0400 AC: 141 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.7
DANN	Benign	0.76
PhyloP100		1.3
PromoterAI		-0.0084	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17814456; hg19: chr8-56986417; COSMIC: COSV50536407; COSMIC: COSV50536407;