chr16-18788063-C-T

Variant names:

• chr16-18788063-C-T
• rs1567287990
• NM_001019.5:c.213G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_001019.5(RPS15A):​c.213G>A​(p.Lys71Lys) variant causes a splice region, synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPS15A NM_001019.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.9922
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.83
• Publications: 0 publications found

Genes affected

RPS15A (HGNC:10389): (ribosomal protein S15a) 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 S8P family of ribosomal proteins. It is located in the cytoplasm. 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]

RPS15A Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Diamond-Blackfan anemia 20

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ENSG00000260342 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
• PP5: Variant 16-18788063-C-T is Pathogenic according to our data. Variant chr16-18788063-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 617665.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001019.5. 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
	RPS15A	NM_001019.5	MANE Select	c.213G>A	p.Lys71Lys	splice_region synonymous	Exon 3 of 5	NP_001010.2
	RPS15A	NM_001030009.2		c.213G>A	p.Lys71Lys	splice_region synonymous	Exon 3 of 5	NP_001025180.1	P62244

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS15A	ENST00000322989.8	TSL:1 MANE Select	c.213G>A	p.Lys71Lys	splice_region synonymous	Exon 3 of 5	ENSP00000318646.4	P62244
	ENSG00000260342	ENST00000567078.2	TSL:3	c.711G>A	p.Lys237Lys	splice_region synonymous	Exon 7 of 7	ENSP00000454746.2	H3BN98
	RPS15A	ENST00000563390.5	TSL:1	c.213G>A	p.Lys71Lys	splice_region synonymous	Exon 3 of 5	ENSP00000457000.1	P62244

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Diamond-Blackfan anemia 20 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Benign	0.91
PhyloP100		7.8
Mutation Taster		=15/85	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.93
SpliceAI score (max)		0.19		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: rs1567287990; hg19: chr16-18799385;