chr19-58387689-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000596046.1(RPS5):​c.-449T>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-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.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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>A		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>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000472985.1
	RPS5	ENST00000596046.1	TSL:1	c.-449T>A		5_prime_UTR	Exon 1 of 5	ENSP00000472985.1
	RPS5	ENST00000196551.8	TSL:1 MANE Select	c.-2+350T>A		intron	N/A	ENSP00000196551.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 19220 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10678

African (AFR) AF: 0.00 AC: 0 AN: 420

American (AMR) AF: 0.00 AC: 0 AN: 2238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 332

East Asian (EAS) AF: 0.00 AC: 0 AN: 716

South Asian (SAS) AF: 0.00 AC: 0 AN: 3998

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 48

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10182

Other (OTH) AF: 0.00 AC: 0 AN: 854

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.0
DANN	Benign	0.79
PhyloP100		0.14
PromoterAI		-0.024	Neutral

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;