14-49577674-T-C

Position:

• chr14-49577674-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001030001.4(RPS29):​c.*138A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 765,400 control chromosomes in the GnomAD database, including 186,032 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (37336 hom., cov: 32)
  • Exomes 𝑓: 0.68 (148696 hom.)
• Consequence: RPS29 NM_001030001.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.90

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]

RPL32P29 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 14-49577674-T-C is Benign according to our data. Variant chr14-49577674-T-C is described in ClinVar as [Benign]. Clinvar id is 1248443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS29	NM_001030001.4	c.*138A>G		3_prime_UTR_variant	3/3		NP_001025172.1
RPL32P29		n.49577674T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS29	ENST00000396020.7	c.*138A>G		3_prime_UTR_variant	3/3	1		ENSP00000379339.3
RPL32P29	ENST00000497398.1	n.121A>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104785 AN: 151976 Hom.: 37299 Cov.: 32

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.681

GnomAD4 exome AF: 0.678 AC: 415928 AN: 613306 Hom.: 148696 Cov.: 7 AF XY: 0.674 AC XY: 223329 AN XY: 331432

Gnomad4 AFR exome AF: 0.659

Gnomad4 AMR exome AF: 0.622

Gnomad4 ASJ exome AF: 0.735

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.549

Gnomad4 FIN exome AF: 0.774

Gnomad4 NFE exome AF: 0.746

Gnomad4 OTH exome AF: 0.685

GnomAD4 genome AF: 0.690 AC: 104877 AN: 152094 Hom.: 37336 Cov.: 32 AF XY: 0.686 AC XY: 51027 AN XY: 74376

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.680

Alfa AF: 0.733 Hom.: 9658

Bravo AF: 0.677

Asia WGS AF: 0.405 AC: 1409 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 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.9
DANN	Benign	0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2883438; hg19: chr14-50044392; COSMIC: COSV68464352;