rs587777568

Variant names:

• chr14-49586021-T-A
• rs587777568
• NM_001032.5:c.91A>T

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_001030001.4(RPS29):​c.91A>T​(p.Ile31Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPS29 NM_001030001.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.51
• Publications: 3 publications found

Genes affected

RPS29 (HGNC:10419): (ribosomal protein S29) 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 and a member of the S14P family of ribosomal proteins. The protein, which contains a C2-C2 zinc finger-like domain that can bind to zinc, can enhance the tumor suppressor activity of Ras-related protein 1A (KREV1). It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2013]

RPS29 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 13

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.885
• PP5: Variant 14-49586021-T-A is Pathogenic according to our data. Variant chr14-49586021-T-A is described in ClinVar as Pathogenic. ClinVar VariationId is 140738.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001030001.4. 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
	RPS29	NM_001032.5	MANE Select	c.91A>T	p.Ile31Phe	missense	Exon 2 of 3	NP_001023.1
	RPS29	NM_001030001.4		c.91A>T	p.Ile31Phe	missense	Exon 2 of 3	NP_001025172.1
	RPS29	NM_001351375.2		c.82A>T	p.Ile28Phe	missense	Exon 2 of 3	NP_001338304.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS29	ENST00000245458.11	TSL:1 MANE Select	c.91A>T	p.Ile31Phe	missense	Exon 2 of 3	ENSP00000245458.7
	RPS29	ENST00000554075.2	TSL:1	c.91A>T	p.Ile31Phe	missense	Exon 2 of 2	ENSP00000496485.1
	RPS29	ENST00000396020.7	TSL:1	c.91A>T	p.Ile31Phe	missense	Exon 2 of 3	ENSP00000379339.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Diamond-Blackfan anemia 13 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.78	D
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.73	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.43	T
PhyloP100		7.5
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.7	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.011	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.24	B
Vest4		0.97
MutPred		0.67		Gain of catalytic residue at L30 (P = 0)
MVP		0.35
MPC		3.0
ClinPred		0.98	D
GERP RS		6.1
PromoterAI		-0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.93
gMVP		0.94
Mutation Taster		=19/81	disease causing (ClinVar)

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: rs587777568; hg19: chr14-50052739;