NM_001032.5:c.163-57G>A

Variant names:

• chr14-49583732-C-T
• rs75067682
• NM_001032.5:c.163-57G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001032.5(RPS29):​c.163-57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00919 in 1,104,492 control chromosomes in the GnomAD database, including 507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (311 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (196 hom.)
• Consequence: RPS29 NM_001032.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.441
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 14-49583732-C-T is Benign according to our data. Variant chr14-49583732-C-T is described in ClinVar as Benign. ClinVar VariationId is 1223950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

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.163-57G>A		intron	N/A	NP_001023.1	P62273-1
	RPS29	NM_001030001.4		c.162+2218G>A		intron	N/A	NP_001025172.1	P62273-2
	RPS29	NM_001351375.2		c.154-57G>A		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.163-57G>A		intron	N/A	ENSP00000245458.7	P62273-1
	RPS29	ENST00000396020.7	TSL:1	c.162+2218G>A		intron	N/A	ENSP00000379339.3	P62273-2
	RPS29	ENST00000556230.2	TSL:1	c.163-57G>A		intron	N/A	ENSP00000495033.1	P62273-1

Frequencies

GnomAD3 genomes AF: 0.0364 AC: 5513 AN: 151382 Hom.: 310 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0201

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000194

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00171

Gnomad OTH AF: 0.0226

GnomAD4 exome AF: 0.00485 AC: 4624 AN: 953004 Hom.: 196 AF XY: 0.00425 AC XY: 2103 AN XY: 494976

African (AFR) AF: 0.122 AC: 2667 AN: 21784

American (AMR) AF: 0.0104 AC: 364 AN: 35160

Ashkenazi Jewish (ASJ) AF: 0.000917 AC: 20 AN: 21816

East Asian (EAS) AF: 0.0000540 AC: 2 AN: 37054

South Asian (SAS) AF: 0.000654 AC: 46 AN: 70300

European-Finnish (FIN) AF: 0.0000383 AC: 2 AN: 52184

Middle Eastern (MID) AF: 0.0187 AC: 84 AN: 4486

European-Non Finnish (NFE) AF: 0.00144 AC: 960 AN: 667124

Other (OTH) AF: 0.0111 AC: 479 AN: 43096

GnomAD4 genome AF: 0.0365 AC: 5523 AN: 151488 Hom.: 311 Cov.: 32 AF XY: 0.0352 AC XY: 2607 AN XY: 74002

African (AFR) AF: 0.122 AC: 5042 AN: 41322

American (AMR) AF: 0.0200 AC: 305 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4812

European-Finnish (FIN) AF: 0.000194 AC: 2 AN: 10304

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.00171 AC: 116 AN: 67892

Other (OTH) AF: 0.0223 AC: 47 AN: 2104

Alfa AF: 0.0252 Hom.: 23

Bravo AF: 0.0411

Asia WGS AF: 0.00837 AC: 29 AN: 3478

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
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.2
DANN	Benign	0.73
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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: rs75067682; hg19: chr14-50050450;