14-49583678-GAAAA-GAA

Variant names:

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

Variant summary

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

The NM_001032.5(RPS29):​c.163-5_163-4delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,016,956 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (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_163-4delTT		splice_region intron	N/A	NP_001023.1	P62273-1
	RPS29	NM_001030001.4		c.162+2270_162+2271delTT		intron	N/A	NP_001025172.1	P62273-2
	RPS29	NM_001351375.2		c.154-5_154-4delTT		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_163-4delTT		splice_region intron	N/A	ENSP00000245458.7	P62273-1
	RPS29	ENST00000396020.7	TSL:1	c.162+2270_162+2271delTT		intron	N/A	ENSP00000379339.3	P62273-2
	RPS29	ENST00000556230.2	TSL:1	c.163-5_163-4delTT		splice_region intron	N/A	ENSP00000495033.1	P62273-1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 138338 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: 0.000294 AC: 26 AN: 88432 AF XY: 0.000189

Gnomad AFR exome AF: 0.000472

Gnomad AMR exome AF: 0.000764

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000153

Gnomad FIN exome AF: 0.000105

Gnomad NFE exome AF: 0.000166

Gnomad OTH exome AF: 0.00100

GnomAD4 exome AF: 0.000198 AC: 201 AN: 1016956 Hom.: 0 AF XY: 0.000181 AC XY: 92 AN XY: 509300

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

African (AFR) AF: 0.000223 AC: 5 AN: 22436

American (AMR) AF: 0.000520 AC: 15 AN: 28836

Ashkenazi Jewish (ASJ) AF: 0.000109 AC: 2 AN: 18268

East Asian (EAS) AF: 0.000109 AC: 3 AN: 27460

South Asian (SAS) AF: 0.000135 AC: 8 AN: 59426

European-Finnish (FIN) AF: 0.0000254 AC: 1 AN: 39368

Middle Eastern (MID) AF: 0.000231 AC: 1 AN: 4328

European-Non Finnish (NFE) AF: 0.000205 AC: 159 AN: 775322

Other (OTH) AF: 0.000169 AC: 7 AN: 41512

⚠️ 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: 138338 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 66718

African (AFR) AF: 0.00 AC: 0 AN: 37648

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: 7890

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63458

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

Alfa AF: 0.000985 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs373877728; hg19: chr14-50050396; COSMIC: COSV55421487; COSMIC: COSV55421487;