14-49583678-GAAAA-G

Variant names:

• chr14-49583678-GAAAA-G
• rs373877728
• NM_001032.5:c.163-7_163-4delTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001032.5(RPS29):​c.163-7_163-4delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPS29 NM_001032.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.808
• Publications: 1 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: Labcorp Genetics (formerly Invitae), PanelApp Australia
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032.5. 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
	RPS29	NM_001032.5	MANE Select	c.163-7_163-4delTTTT		splice_region intron	N/A	NP_001023.1	P62273-1
	RPS29	NM_001030001.4		c.162+2268_162+2271delTTTT		intron	N/A	NP_001025172.1	P62273-2
	RPS29	NM_001351375.2		c.154-7_154-4delTTTT		splice_region intron	N/A	NP_001338304.1	A0A087WTT6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS29	ENST00000245458.11	TSL:1 MANE Select	c.163-7_163-4delTTTT		splice_region intron	N/A	ENSP00000245458.7	P62273-1
	RPS29	ENST00000396020.7	TSL:1	c.162+2268_162+2271delTTTT		intron	N/A	ENSP00000379339.3	P62273-2
	RPS29	ENST00000556230.2	TSL:1	c.163-7_163-4delTTTT		splice_region intron	N/A	ENSP00000495033.1	P62273-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1021072 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 511376

African (AFR) AF: 0.00 AC: 0 AN: 22522

American (AMR) AF: 0.00 AC: 0 AN: 29020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18360

East Asian (EAS) AF: 0.00 AC: 0 AN: 27594

South Asian (SAS) AF: 0.00 AC: 0 AN: 59720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39488

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4336

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 778344

Other (OTH) AF: 0.00 AC: 0 AN: 41688

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.56		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.56		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs373877728; hg19: chr14-50050396;