19-1440091-C-T

Variant names:

• chr19-1440091-C-T
• rs778995103
• NM_001018.5:c.162C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001018.5(RPS15):​c.162C>T​(p.His54His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000213 in 1,583,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: RPS15 NM_001018.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.54

Genes affected

RPS15 (HGNC:10388): (ribosomal protein S15) 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 S19P family of ribosomal proteins. It is located in the cytoplasm. This gene has been found to be activated in various tumors, such as insulinomas, esophageal cancers, and colon cancers. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 19-1440091-C-T is Benign according to our data. Variant chr19-1440091-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3048640.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.54 with no splicing effect.
• BS2: High AC in GnomAd4 at 51 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS15	NM_001018.5	c.162C>T	p.His54His	synonymous_variant	Exon 3 of 4	ENST00000592588.7	NP_001009.1
RPS15	NM_001308226.2	c.183C>T	p.His61His	synonymous_variant	Exon 3 of 4		NP_001295155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS15	ENST00000592588.7	c.162C>T	p.His54His	synonymous_variant	Exon 3 of 4	1	NM_001018.5	ENSP00000467466.3

Frequencies

GnomAD3 genomes AF: 0.000335 AC: 51 AN: 152268 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000964

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000302 AC: 58 AN: 192314 AF XY: 0.000308

Gnomad AFR exome AF: 0.000193

Gnomad AMR exome AF: 0.000743

Gnomad ASJ exome AF: 0.00136

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000190

Gnomad OTH exome AF: 0.00121

GnomAD4 exome AF: 0.000201 AC: 287 AN: 1431158 Hom.: 0 Cov.: 33 AF XY: 0.000199 AC XY: 141 AN XY: 708634

Gnomad4 AFR exome AF: 0.000421 AC: 14 AN: 33228

Gnomad4 AMR exome AF: 0.00102 AC: 39 AN: 38236

Gnomad4 ASJ exome AF: 0.00201 AC: 51 AN: 25428

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 38706

Gnomad4 SAS exome AF: 0.000110 AC: 9 AN: 81928

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 50596

Gnomad4 NFE exome AF: 0.000112 AC: 123 AN: 1098716

Gnomad4 Remaining exome AF: 0.000640 AC: 38 AN: 59376

GnomAD4 genome AF: 0.000335 AC: 51 AN: 152268 Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29 AN XY: 74392

Gnomad4 AFR AF: 0.0000964 AC: 0.0000964413 AN: 0.0000964413

Gnomad4 AMR AF: 0.00164 AC: 0.00163527 AN: 0.00163527

Gnomad4 ASJ AF: 0.000864 AC: 0.000864055 AN: 0.000864055

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000250 AC: 0.000249816 AN: 0.000249816

Gnomad4 OTH AF: 0.000955 AC: 0.00095511 AN: 0.00095511

Alfa AF: 0.000541 Hom.: 0

Bravo AF: 0.000370

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

RPS15-related disorder Benign:1

Sep 27, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	-0.57
CADD	Benign	10
DANN	Benign	0.90
Mutation Taster		=95/5	polymorphism

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: rs778995103; hg19: chr19-1440090;