chr14-49583732-C-T

Position:

• chr14-49583732-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS29	NM_001032.5	c.163-57G>A		intron_variant		ENST00000245458.11	NP_001023.1
RPS29	NM_001030001.4	c.162+2218G>A		intron_variant			NP_001025172.1
RPS29	NM_001351375.2	c.154-57G>A		intron_variant			NP_001338304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS29	ENST00000245458.11	c.163-57G>A		intron_variant		1	NM_001032.5	ENSP00000245458.7

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

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.0104

Gnomad4 ASJ exome AF: 0.000917

Gnomad4 EAS exome AF: 0.0000540

Gnomad4 SAS exome AF: 0.000654

Gnomad4 FIN exome AF: 0.0000383

Gnomad4 NFE exome AF: 0.00144

Gnomad4 OTH exome AF: 0.0111

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

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0200

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.000194

Gnomad4 NFE AF: 0.00171

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0213 Hom.: 17

Bravo AF: 0.0411

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 05, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.2
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs75067682; hg19: chr14-50050450;