6-33272922-G-T

Position:

• chr6-33272922-G-T

Variant summary

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

The NM_022551.3(RPS18):​c.102+196G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,212 control chromosomes in the GnomAD database, including 1,323 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 0.13 (1323 hom., cov: 33)
• Consequence: RPS18 NM_022551.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163

Genes affected

RPS18 (HGNC:10401): (ribosomal protein S18) 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 S13P family of ribosomal proteins. It is located in the cytoplasm. The gene product of the E. coli ortholog (ribosomal protein S13) is involved in the binding of fMet-tRNA, and thus, in the initiation of translation. This gene is an ortholog of mouse Ke3. 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS18	NM_022551.3	c.102+196G>T		intron_variant		ENST00000439602.7	NP_072045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS18	ENST00000439602.7	c.102+196G>T		intron_variant		1	NM_022551.3	ENSP00000393241	P1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19072 AN: 152094 Hom.: 1320 Cov.: 33

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.0811

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.0837

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.162

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.125 AC: 19087 AN: 152212 Hom.: 1323 Cov.: 33 AF XY: 0.124 AC XY: 9225 AN XY: 74400

Gnomad4 AFR AF: 0.0800

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.0809

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.0837

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.166

Alfa AF: 0.143 Hom.: 1009

Bravo AF: 0.126

Asia WGS AF: 0.176 AC: 613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs466886; hg19: chr6-33240699;