NM_001018.5:c.162C>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
• Publications: 0 publications found

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]

RPS15 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS15	NM_001018.5	MANE Select	c.162C>T	p.His54His	synonymous	Exon 3 of 4	NP_001009.1	P62841
	RPS15	NM_001308226.2		c.183C>T	p.His61His	synonymous	Exon 3 of 4	NP_001295155.1	K7ELC2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS15	ENST00000592588.7	TSL:1 MANE Select	c.162C>T	p.His54His	synonymous	Exon 3 of 4	ENSP00000467466.3	P62841
	RPS15	ENST00000592623.5	TSL:1	c.81C>T	p.His27His	synonymous	Exon 2 of 3	ENSP00000474433.2	A0A0B4J2B4
	RPS15	ENST00000593052.5	TSL:2	c.183C>T	p.His61His	synonymous	Exon 3 of 4	ENSP00000466010.1	K7ELC2

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

African (AFR) AF: 0.000421 AC: 14 AN: 33228

American (AMR) AF: 0.00102 AC: 39 AN: 38236

Ashkenazi Jewish (ASJ) AF: 0.00201 AC: 51 AN: 25428

East Asian (EAS) AF: 0.00 AC: 0 AN: 38706

South Asian (SAS) AF: 0.000110 AC: 9 AN: 81928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50596

Middle Eastern (MID) AF: 0.00263 AC: 13 AN: 4944

European-Non Finnish (NFE) AF: 0.000112 AC: 123 AN: 1098716

Other (OTH) 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

African (AFR) AF: 0.0000964 AC: 4 AN: 41476

American (AMR) AF: 0.00164 AC: 25 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68050

Other (OTH) AF: 0.000955 AC: 2 AN: 2094

Alfa AF: 0.000541 Hom.: 0

Bravo AF: 0.000370

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	RPS15-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	10
DANN	Benign	0.90
PhyloP100		1.5
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

Other links and lift over

dbSNP: rs778995103; hg19: chr19-1440090;