NM_001032.5:c.163-4dupT

Variant names:

• chr14-49583678-G-GA
• rs373877728
• NM_001032.5:c.163-4dupT

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_001032.5(RPS29):​c.163-4dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0756 in 1,010,158 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.088 (0 hom.)
• Consequence: RPS29 NM_001032.5 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -12 ACMG points.

• BP6: Variant 14-49583678-G-GA is Benign according to our data. Variant chr14-49583678-G-GA is described in ClinVar as Benign. ClinVar VariationId is 1248271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 56 AD gene.

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

Frequencies

GnomAD3 genomes AF: 0.000405 AC: 56 AN: 138168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000218

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00216

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.000532

GnomAD2 exomes AF: 0.0964 AC: 8522 AN: 88432 AF XY: 0.0957

Gnomad AFR exome AF: 0.0803

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.150

Gnomad EAS exome AF: 0.123

Gnomad FIN exome AF: 0.0321

Gnomad NFE exome AF: 0.0831

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.0875 AC: 76299 AN: 871940 Hom.: 0 Cov.: 18 AF XY: 0.0884 AC XY: 38063 AN XY: 430436

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

African (AFR) AF: 0.0902 AC: 1752 AN: 19432

American (AMR) AF: 0.0945 AC: 2279 AN: 24128

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 1485 AN: 13972

East Asian (EAS) AF: 0.104 AC: 2159 AN: 20736

South Asian (SAS) AF: 0.109 AC: 4893 AN: 45060

European-Finnish (FIN) AF: 0.0700 AC: 2089 AN: 29838

Middle Eastern (MID) AF: 0.0640 AC: 241 AN: 3766

European-Non Finnish (NFE) AF: 0.0855 AC: 58173 AN: 680584

Other (OTH) AF: 0.0938 AC: 3228 AN: 34424

⚠️ 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 AF: 0.000405 AC: 56 AN: 138218 Hom.: 0 Cov.: 32 AF XY: 0.000360 AC XY: 24 AN XY: 66684

African (AFR) AF: 0.000212 AC: 8 AN: 37712

American (AMR) AF: 0.000218 AC: 3 AN: 13744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3272

East Asian (EAS) AF: 0.00 AC: 0 AN: 4808

South Asian (SAS) AF: 0.00 AC: 0 AN: 4414

European-Finnish (FIN) AF: 0.00216 AC: 17 AN: 7854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.000426 AC: 27 AN: 63384

Other (OTH) AF: 0.000529 AC: 1 AN: 1892

Alfa AF: 0.0492 Hom.: 1

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism

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: rs373877728; hg19: chr14-50050396; COSMIC: COSV55421572; COSMIC: COSV55421572;