15-82540294-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001021.6(RPS17):c.3+132C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0472 in 1,586,162 control chromosomes in the GnomAD database, including 2,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.074 (639 hom., cov: 33)
  • Exomes 𝑓: 0.044 (1917 hom.)
• Consequence: RPS17 NM_001021.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.168

Genes affected

RPS17 (HGNC:10397): (ribosomal protein S17) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of four 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 S17E family of ribosomal proteins and is located in the cytoplasm. Mutations in this gene cause Diamond-Blackfan anemia 4. Alternative splicing of this gene results in multiple transcript variants. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-82540294-G-C is Benign according to our data. Variant chr15-82540294-G-C is described in ClinVar as [Benign]. Clinvar id is 1235999.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS17	NM_001021.6	c.3+132C>G		intron_variant		ENST00000647841.1
RPS17	NR_111943.2	n.164C>G		non_coding_transcript_exon_variant	1/4
RPS17	NR_111944.3	n.32+132C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS17	ENST00000647841.1	c.3+132C>G		intron_variant			NM_001021.6	P1

Frequencies

GnomAD3 genomes AF: 0.0743 AC: 11313 AN: 152174 Hom.: 637 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0718

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.0503

Gnomad FIN AF: 0.0551

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0402

Gnomad OTH AF: 0.0674

GnomAD4 exome AF: 0.0443 AC: 63458 AN: 1433870 Hom.: 1917 Cov.: 31 AF XY: 0.0435 AC XY: 30947 AN XY: 711546

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.0973

Gnomad4 ASJ exome AF: 0.0448

Gnomad4 EAS exome AF: 0.00100

Gnomad4 SAS exome AF: 0.0440

Gnomad4 FIN exome AF: 0.0550

Gnomad4 NFE exome AF: 0.0396

Gnomad4 OTH exome AF: 0.0487

GnomAD4 genome AF: 0.0744 AC: 11330 AN: 152292 Hom.: 639 Cov.: 33 AF XY: 0.0737 AC XY: 5488 AN XY: 74470

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0717

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0497

Gnomad4 FIN AF: 0.0551

Gnomad4 NFE AF: 0.0402

Gnomad4 OTH AF: 0.0667

Alfa AF: 0.00750 Hom.: 10

Bravo AF: 0.0807

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 15, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.66

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: rs542153649; hg19: chr15-83209045;