rs1049218128

Variant names:

• chr15-82538321-T-C
• rs1049218128
• NM_001021.6:c.312A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-82538321-T-C
• chr15-82538321-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001021.6(RPS17):​c.312A>G​(p.Glu104Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00412 in 1,613,404 control chromosomes in the GnomAD database, including 239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (123 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (116 hom.)
• Consequence: RPS17 NM_001021.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0510
• Publications: 0 publications found

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]

RPS17 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 4

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000260836 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 15-82538321-T-C is Benign according to our data. Variant chr15-82538321-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1223515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.051 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0737 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001021.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS17	NM_001021.6	MANE Select	c.312A>G	p.Glu104Glu	synonymous	Exon 4 of 5	NP_001012.1	P08708
	RPS17	NR_111943.2		n.634A>G		non_coding_transcript_exon	Exon 3 of 4
	RPS17	NR_111944.3		n.341A>G		non_coding_transcript_exon	Exon 4 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS17	ENST00000647841.1	MANE Select	c.312A>G	p.Glu104Glu	synonymous	Exon 4 of 5	ENSP00000498019.1	P08708
	ENSG00000260836	ENST00000562833.2	TSL:3	c.1659A>G	p.Glu553Glu	synonymous	Exon 12 of 13	ENSP00000454786.2	H3BNC9
	RPS17	ENST00000561157.5	TSL:2	c.312A>G	p.Glu104Glu	synonymous	Exon 4 of 4	ENSP00000453910.1	H0YN88

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3363 AN: 152172 Hom.: 123 Cov.: 32

Gnomad AFR AF: 0.0761

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00225 AC: 3289 AN: 1461114 Hom.: 116 Cov.: 31 AF XY: 0.00190 AC XY: 1381 AN XY: 726882

African (AFR) AF: 0.0783 AC: 2620 AN: 33448

American (AMR) AF: 0.00445 AC: 199 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00221 AC: 12 AN: 5438

European-Non Finnish (NFE) AF: 0.000137 AC: 152 AN: 1111760

Other (OTH) AF: 0.00469 AC: 283 AN: 60330

GnomAD4 genome AF: 0.0221 AC: 3361 AN: 152290 Hom.: 123 Cov.: 32 AF XY: 0.0216 AC XY: 1605 AN XY: 74468

African (AFR) AF: 0.0759 AC: 3152 AN: 41542

American (AMR) AF: 0.0101 AC: 155 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68026

Other (OTH) AF: 0.0137 AC: 29 AN: 2112

Alfa AF: 0.0184 Hom.: 5

Bravo AF: 0.0260

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Diamond-Blackfan anemia (1)
-	-	1	Diamond-Blackfan anemia 4 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.9
DANN	Benign	0.91
PhyloP100		-0.051
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7

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

Other links and lift over

dbSNP: rs1049218128; hg19: chr15-83207072;