5-150447626-G-C

Position:

• chr5-150447626-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_005617.4(RPS14):​c.108C>G​(p.Ser36Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,613,904 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.010 (32 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (30 hom.)
• Consequence: RPS14 NM_005617.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.74

Genes affected

RPS14 (HGNC:10387): (ribosomal protein S14) 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 S11P family of ribosomal proteins. It is located in the cytoplasm. Transcript variants utilizing alternative transcription initiation sites have been described in the literature. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. In Chinese hamster ovary cells, mutations in this gene can lead to resistance to emetine, a protein synthesis inhibitor. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

RPS14 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 5-150447626-G-C is Benign according to our data. Variant chr5-150447626-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3352911.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.74 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0102 (1559/152296) while in subpopulation AFR AF= 0.0356 (1478/41548). AF 95% confidence interval is 0.0341. There are 32 homozygotes in gnomad4. There are 746 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1559 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS14	NM_005617.4	c.108C>G	p.Ser36Ser	synonymous_variant	2/5	ENST00000407193.7	NP_005608.1
RPS14	NM_001025070.2	c.108C>G	p.Ser36Ser	synonymous_variant	2/5		NP_001020241.1
RPS14	NM_001025071.2	c.108C>G	p.Ser36Ser	synonymous_variant	2/5		NP_001020242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS14	ENST00000407193.7	c.108C>G	p.Ser36Ser	synonymous_variant	2/5	2	NM_005617.4	ENSP00000385425.1

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1545 AN: 152178 Hom.: 31 Cov.: 33

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00909

GnomAD3 exomes AF: 0.00273 AC: 687 AN: 251434 Hom.: 19 AF XY: 0.00213 AC XY: 290 AN XY: 135886

Gnomad AFR exome AF: 0.0367

Gnomad AMR exome AF: 0.00199

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00112 AC: 1643 AN: 1461608 Hom.: 30 Cov.: 31 AF XY: 0.000935 AC XY: 680 AN XY: 727116

Gnomad4 AFR exome AF: 0.0364

Gnomad4 AMR exome AF: 0.00212

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000121

Gnomad4 OTH exome AF: 0.00295

GnomAD4 genome AF: 0.0102 AC: 1559 AN: 152296 Hom.: 32 Cov.: 33 AF XY: 0.0100 AC XY: 746 AN XY: 74462

Gnomad4 AFR AF: 0.0356

Gnomad4 AMR AF: 0.00359

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.000731 Hom.: 0

Bravo AF: 0.0113

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

RPS14-related condition Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 25, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

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: rs112432829; hg19: chr5-149827189;