ENST00000596046.1:c.-449T>C

Variant names:

• chr19-58387689-T-C
• rs893179
• ENST00000596046.1:c.-449T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000596046.1(RPS5):​c.-449T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 171,276 control chromosomes in the GnomAD database, including 21,357 homozygotes. 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: 𝑓 0.49 (19442 hom., cov: 34)
  • Exomes 𝑓: 0.43 (1915 hom.)
• Consequence: RPS5 ENST00000596046.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• Publications: 21 publications found

Genes affected

RPS5 (HGNC:10426): (ribosomal protein S5) 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 S7P 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, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ENSG00000294853 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000596046.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS5	NM_001009.4	MANE Select	c.-2+350T>C		intron	N/A	NP_001000.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS5	ENST00000596046.1	TSL:1	c.-449T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000472985.1
	RPS5	ENST00000596046.1	TSL:1	c.-449T>C		5_prime_UTR	Exon 1 of 5	ENSP00000472985.1
	RPS5	ENST00000196551.8	TSL:1 MANE Select	c.-2+350T>C		intron	N/A	ENSP00000196551.3

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74628 AN: 152014 Hom.: 19407 Cov.: 34

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.510

GnomAD4 exome AF: 0.431 AC: 8253 AN: 19144 Hom.: 1915 Cov.: 0 AF XY: 0.437 AC XY: 4646 AN XY: 10636

African (AFR) AF: 0.708 AC: 296 AN: 418

American (AMR) AF: 0.479 AC: 1068 AN: 2228

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 164 AN: 330

East Asian (EAS) AF: 0.492 AC: 352 AN: 716

South Asian (SAS) AF: 0.431 AC: 1717 AN: 3982

European-Finnish (FIN) AF: 0.407 AC: 176 AN: 432

Middle Eastern (MID) AF: 0.583 AC: 28 AN: 48

European-Non Finnish (NFE) AF: 0.401 AC: 4062 AN: 10138

Other (OTH) AF: 0.458 AC: 390 AN: 852

GnomAD4 genome AF: 0.491 AC: 74718 AN: 152132 Hom.: 19442 Cov.: 34 AF XY: 0.492 AC XY: 36565 AN XY: 74340

African (AFR) AF: 0.666 AC: 27663 AN: 41522

American (AMR) AF: 0.501 AC: 7649 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1654 AN: 3468

East Asian (EAS) AF: 0.498 AC: 2574 AN: 5166

South Asian (SAS) AF: 0.459 AC: 2212 AN: 4822

European-Finnish (FIN) AF: 0.401 AC: 4238 AN: 10560

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27352 AN: 67994

Other (OTH) AF: 0.508 AC: 1073 AN: 2112

Alfa AF: 0.439 Hom.: 18982

Bravo AF: 0.506

Asia WGS AF: 0.450 AC: 1569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.73
PhyloP100		0.14
PromoterAI		-0.034	Neutral
Mutation Taster		=298/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs893179; hg19: chr19-58899056;