11-17077484-A-G

Position:

• chr11-17077484-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001017.3(RPS13):​c.24-7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,613,924 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0023 (12 hom.)
• Consequence: RPS13 NM_001017.3 splice_region, intron
• Scores: Splicing: ADA: 0.0005039
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.40

Genes affected

RPS13 (HGNC:10386): (ribosomal protein S13) 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. The protein belongs to the S15P family of ribosomal proteins. It is located in the cytoplasm. The protein has been shown to bind to the 5.8S rRNA in rat. The gene product of the E. coli ortholog (ribosomal protein S15) functions at early steps in ribosome assembly. This gene is co-transcribed with two U14 small nucleolar RNA genes, which are located in its third and fifth introns. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPS13 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 11-17077484-A-G is Benign according to our data. Variant chr11-17077484-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2641639.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS13	NM_001017.3	c.24-7T>C		splice_region_variant, intron_variant		ENST00000525634.6	NP_001008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS13	ENST00000525634.6	c.24-7T>C		splice_region_variant, intron_variant		1	NM_001017.3	ENSP00000435777.1

Frequencies

GnomAD3 genomes AF: 0.00215 AC: 327 AN: 152028 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00244

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00264 AC: 661 AN: 250822 Hom.: 4 AF XY: 0.00262 AC XY: 355 AN XY: 135648

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.0272

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000686

Gnomad FIN exome AF: 0.0000929

Gnomad NFE exome AF: 0.00248

Gnomad OTH exome AF: 0.00344

GnomAD4 exome AF: 0.00228 AC: 3337 AN: 1461778 Hom.: 12 Cov.: 31 AF XY: 0.00230 AC XY: 1672 AN XY: 727196

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.00184

Gnomad4 ASJ exome AF: 0.0262

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000893

Gnomad4 FIN exome AF: 0.000318

Gnomad4 NFE exome AF: 0.00200

Gnomad4 OTH exome AF: 0.00343

GnomAD4 genome AF: 0.00215 AC: 327 AN: 152146 Hom.: 1 Cov.: 31 AF XY: 0.00195 AC XY: 145 AN XY: 74388

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.000661

Gnomad4 NFE AF: 0.00244

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00373 Hom.: 0

Bravo AF: 0.00216

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00376

EpiControl AF: 0.00368

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

RPS13: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00050
dbscSNV1_RF	Benign	0.092
SpliceAI score (max)		0.010		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: rs74416259; hg19: chr11-17099031;