14-49583678-GAAAA-GAAAAAA

Variant names:

• chr14-49583678-G-GAA
• rs373877728
• NM_001032.5:c.163-5_163-4dupTT

Variant summary

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

The NM_001032.5(RPS29):​c.163-5_163-4dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPS29 NM_001032.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536
• 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 0 ACMG points.

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.163-5_163-4dupTT		splice_region intron	N/A	NP_001023.1	P62273-1
	RPS29	NM_001030001.4		c.162+2270_162+2271dupTT		intron	N/A	NP_001025172.1	P62273-2
	RPS29	NM_001351375.2		c.154-5_154-4dupTT		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.163-5_163-4dupTT		splice_region intron	N/A	ENSP00000245458.7	P62273-1
	RPS29	ENST00000396020.7	TSL:1	c.162+2270_162+2271dupTT		intron	N/A	ENSP00000379339.3	P62273-2
	RPS29	ENST00000556230.2	TSL:1	c.163-5_163-4dupTT		splice_region intron	N/A	ENSP00000495033.1	P62273-1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 138348 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000498 AC: 44 AN: 88432 AF XY: 0.000484

Gnomad AFR exome AF: 0.00126

Gnomad AMR exome AF: 0.000764

Gnomad ASJ exome AF: 0.000654

Gnomad EAS exome AF: 0.000916

Gnomad FIN exome AF: 0.000105

Gnomad NFE exome AF: 0.000284

Gnomad OTH exome AF: 0.000501

GnomAD4 exome AF: 0.000364 AC: 370 AN: 1016184 Hom.: 0 Cov.: 18 AF XY: 0.000314 AC XY: 160 AN XY: 508922

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000581 AC: 13 AN: 22374

American (AMR) AF: 0.000242 AC: 7 AN: 28868

Ashkenazi Jewish (ASJ) AF: 0.000164 AC: 3 AN: 18254

East Asian (EAS) AF: 0.000182 AC: 5 AN: 27436

South Asian (SAS) AF: 0.000287 AC: 17 AN: 59324

European-Finnish (FIN) AF: 0.000127 AC: 5 AN: 39352

Middle Eastern (MID) AF: 0.000231 AC: 1 AN: 4324

European-Non Finnish (NFE) AF: 0.000390 AC: 302 AN: 774790

Other (OTH) AF: 0.000410 AC: 17 AN: 41462

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 138348 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 66728

African (AFR) AF: 0.00 AC: 0 AN: 37650

American (AMR) AF: 0.00 AC: 0 AN: 13760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3278

East Asian (EAS) AF: 0.00 AC: 0 AN: 4828

South Asian (SAS) AF: 0.00 AC: 0 AN: 4432

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63462

Other (OTH) AF: 0.00 AC: 0 AN: 1880

Alfa AF: 0.00131 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.54

Splicing

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

Other links and lift over

dbSNP: rs373877728; hg19: chr14-50050396;