NM_001032.5:c.163-17T>C

Variant names:

• chr14-49583692-A-G
• rs747830198
• NM_001032.5:c.163-17T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001032.5(RPS29):​c.163-17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000801 in 1,385,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000079 (0 hom.)
• Consequence: RPS29 NM_001032.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.476
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 14-49583692-A-G is Benign according to our data. Variant chr14-49583692-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2423256.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 14 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.163-17T>C		intron	N/A	NP_001023.1	P62273-1
	RPS29	NM_001030001.4		c.162+2258T>C		intron	N/A	NP_001025172.1	P62273-2
	RPS29	NM_001351375.2		c.154-17T>C		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.163-17T>C		intron	N/A	ENSP00000245458.7	P62273-1
	RPS29	ENST00000396020.7	TSL:1	c.162+2258T>C		intron	N/A	ENSP00000379339.3	P62273-2
	RPS29	ENST00000556230.2	TSL:1	c.163-17T>C		intron	N/A	ENSP00000495033.1	P62273-1

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 152056 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000342 AC: 8 AN: 234056 AF XY: 0.0000236

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000194

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000184

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000786 AC: 97 AN: 1233506 Hom.: 0 Cov.: 18 AF XY: 0.0000721 AC XY: 45 AN XY: 623778

African (AFR) AF: 0.00 AC: 0 AN: 28178

American (AMR) AF: 0.000150 AC: 6 AN: 40088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24326

East Asian (EAS) AF: 0.00 AC: 0 AN: 38592

South Asian (SAS) AF: 0.00 AC: 0 AN: 77362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5262

European-Non Finnish (NFE) AF: 0.0000995 AC: 91 AN: 914240

Other (OTH) AF: 0.00 AC: 0 AN: 52384

GnomAD4 genome AF: 0.0000921 AC: 14 AN: 152056 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74244

African (AFR) AF: 0.0000241 AC: 1 AN: 41416

American (AMR) AF: 0.000786 AC: 12 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.0000453

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.96
DANN	Benign	0.88
PhyloP100		-0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs747830198; hg19: chr14-50050410;