19-58387689-T-C

Position:

• chr19-58387689-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000596046.1(RPS5):​c.-449T>C variant causes a 5 prime UTR 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS5	NM_001009.4	c.-2+350T>C		intron_variant		ENST00000196551.8	NP_001000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS5	ENST00000196551.8	c.-2+350T>C		intron_variant		1	NM_001009.4	ENSP00000196551	P1

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

Gnomad4 AFR exome AF: 0.708

Gnomad4 AMR exome AF: 0.479

Gnomad4 ASJ exome AF: 0.497

Gnomad4 EAS exome AF: 0.492

Gnomad4 SAS exome AF: 0.431

Gnomad4 FIN exome AF: 0.407

Gnomad4 NFE exome AF: 0.401

Gnomad4 OTH exome AF: 0.458

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

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.508

Alfa AF: 0.430 Hom.: 13867

Bravo AF: 0.506

Asia WGS AF: 0.450 AC: 1569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs893179; hg19: chr19-58899056;