14-49583678-GA-G

Position:

• chr14-49583678-GA-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001032.5(RPS29):​c.163-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,085,416 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.022 (0 hom.)
• Consequence: RPS29 NM_001032.5 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.536

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 -16 ACMG points.

• BP6: Variant 14-49583678-GA-G is Benign according to our data. Variant chr14-49583678-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 1293204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-49583678-GA-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0217 (20593/947108) while in subpopulation AMR AF= 0.0332 (862/25944). AF 95% confidence interval is 0.0314. There are 0 homozygotes in gnomad4_exome. There are 10096 alleles in male gnomad4_exome subpopulation. Median coverage is 18. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS29	NM_001032.5	c.163-4delT		splice_region_variant, intron_variant		ENST00000245458.11	NP_001023.1
RPS29	NM_001030001.4	c.162+2271delT		intron_variant			NP_001025172.1
RPS29	NM_001351375.2	c.154-4delT		splice_region_variant, intron_variant			NP_001338304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS29	ENST00000245458.11	c.163-4delT		splice_region_variant, intron_variant		1	NM_001032.5	ENSP00000245458.7

Frequencies

GnomAD3 genomes AF: 0.000239 AC: 33 AN: 138254 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000291

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000677

Gnomad FIN AF: 0.00127

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000173

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0466 AC: 4120 AN: 88432 Hom.: 0 AF XY: 0.0457 AC XY: 2171 AN XY: 47522

Gnomad AFR exome AF: 0.0388

Gnomad AMR exome AF: 0.0657

Gnomad ASJ exome AF: 0.0628

Gnomad EAS exome AF: 0.0496

Gnomad SAS exome AF: 0.0486

Gnomad FIN exome AF: 0.0221

Gnomad NFE exome AF: 0.0464

Gnomad OTH exome AF: 0.0471

GnomAD4 exome AF: 0.0217 AC: 20593 AN: 947108 Hom.: 0 Cov.: 18 AF XY: 0.0214 AC XY: 10096 AN XY: 472028

Gnomad4 AFR exome AF: 0.0245

Gnomad4 AMR exome AF: 0.0332

Gnomad4 ASJ exome AF: 0.0248

Gnomad4 EAS exome AF: 0.0209

Gnomad4 SAS exome AF: 0.0220

Gnomad4 FIN exome AF: 0.0172

Gnomad4 NFE exome AF: 0.0214

Gnomad4 OTH exome AF: 0.0228

GnomAD4 genome AF: 0.000239 AC: 33 AN: 138308 Hom.: 0 Cov.: 32 AF XY: 0.000210 AC XY: 14 AN XY: 66754

Gnomad4 AFR AF: 0.000159

Gnomad4 AMR AF: 0.000290

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000453

Gnomad4 FIN AF: 0.00127

Gnomad4 NFE AF: 0.000173

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 21, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 08, 2020	- -

Diamond-Blackfan anemia 13 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 13, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs373877728; hg19: chr14-50050396;