19-54207461-C-T

Variant names:

• chr19-54207461-C-T
• rs4838
• NM_001013.4:c.471C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_001013.4(RPS9):​c.471C>T​(p.Ile157Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 1,613,614 control chromosomes in the GnomAD database, including 4,463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.038 (261 hom., cov: 32)
  • Exomes 𝑓: 0.047 (4202 hom.)
• Consequence: RPS9 NM_001013.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.328
• Publications: 14 publications found

Genes affected

RPS9 (HGNC:10442): (ribosomal protein S9) 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 S4P family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, multiple processed pseudogenes derived from this gene are dispersed through the genome. [provided by RefSeq, Jul 2008]

ENSG00000300077 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 19-54207461-C-T is Benign according to our data. Variant chr19-54207461-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056073.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.328 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013.4. 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
	RPS9	NM_001013.4	MANE Select	c.471C>T	p.Ile157Ile	synonymous	Exon 5 of 5	NP_001004.2
	RPS9	NM_001321701.2		c.471C>T	p.Ile157Ile	synonymous	Exon 5 of 5	NP_001308630.1	P46781
	RPS9	NM_001321702.2		c.471C>T	p.Ile157Ile	synonymous	Exon 5 of 5	NP_001308631.1	P46781

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS9	ENST00000302907.9	TSL:1 MANE Select	c.471C>T	p.Ile157Ile	synonymous	Exon 5 of 5	ENSP00000302896.4	P46781
	RPS9	ENST00000391753.6	TSL:1	c.471C>T	p.Ile157Ile	synonymous	Exon 4 of 4	ENSP00000375633.2	P46781
	RPS9	ENST00000441429.1	TSL:1	c.*935C>T		3_prime_UTR	Exon 3 of 3	ENSP00000414314.1	C9JM19

Frequencies

GnomAD3 genomes AF: 0.0376 AC: 5719 AN: 152140 Hom.: 260 Cov.: 32

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0353

Gnomad OTH AF: 0.0445

GnomAD2 exomes AF: 0.0613 AC: 15364 AN: 250714 AF XY: 0.0742

Gnomad AFR exome AF: 0.0185

Gnomad AMR exome AF: 0.0223

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.00174

Gnomad FIN exome AF: 0.00933

Gnomad NFE exome AF: 0.0380

Gnomad OTH exome AF: 0.0580

GnomAD4 exome AF: 0.0470 AC: 68723 AN: 1461356 Hom.: 4202 Cov.: 32 AF XY: 0.0540 AC XY: 39238 AN XY: 726968

African (AFR) AF: 0.0198 AC: 662 AN: 33470

American (AMR) AF: 0.0230 AC: 1027 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 3523 AN: 26128

East Asian (EAS) AF: 0.00111 AC: 44 AN: 39700

South Asian (SAS) AF: 0.259 AC: 22328 AN: 86198

European-Finnish (FIN) AF: 0.0107 AC: 573 AN: 53416

Middle Eastern (MID) AF: 0.144 AC: 784 AN: 5462

European-Non Finnish (NFE) AF: 0.0328 AC: 36504 AN: 1111924

Other (OTH) AF: 0.0543 AC: 3278 AN: 60348

GnomAD4 genome AF: 0.0376 AC: 5720 AN: 152258 Hom.: 261 Cov.: 32 AF XY: 0.0410 AC XY: 3052 AN XY: 74440

African (AFR) AF: 0.0190 AC: 790 AN: 41550

American (AMR) AF: 0.0353 AC: 540 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3470

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5178

South Asian (SAS) AF: 0.255 AC: 1227 AN: 4820

European-Finnish (FIN) AF: 0.0106 AC: 112 AN: 10610

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0353 AC: 2399 AN: 68014

Other (OTH) AF: 0.0441 AC: 93 AN: 2110

Alfa AF: 0.0382 Hom.: 83

Bravo AF: 0.0334

Asia WGS AF: 0.113 AC: 393 AN: 3478

EpiCase AF: 0.0455

EpiControl AF: 0.0467

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	RPS9-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	6.6
DANN	Benign	0.92
PhyloP100		-0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs4838; hg19: chr19-54711329; COSMIC: COSV57189698; COSMIC: COSV57189698;