15-82538982-A-G

Variant names:

• chr15-82538982-A-G
• rs6991
• NM_001021.6:c.159T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001021.6(RPS17):​c.159T>C​(p.Tyr53Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.306 in 1,613,126 control chromosomes in the GnomAD database, including 78,142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.26 (5746 hom., cov: 32)
  • Exomes 𝑓: 0.31 (72396 hom.)
• Consequence: RPS17 NM_001021.6 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 3.74
• Publications: 5 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 15-82538982-A-G is Benign according to our data. Variant chr15-82538982-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 419839.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.401 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.159T>C	p.Tyr53Tyr	synonymous	Exon 3 of 5	NP_001012.1	P08708
	RPS17	NR_111943.2		n.481T>C		non_coding_transcript_exon	Exon 2 of 4
	RPS17	NR_111944.3		n.188T>C		non_coding_transcript_exon	Exon 3 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS17	ENST00000647841.1	MANE Select	c.159T>C	p.Tyr53Tyr	synonymous	Exon 3 of 5	ENSP00000498019.1	P08708
	ENSG00000260836	ENST00000562833.2	TSL:3	c.1506T>C	p.Tyr502Tyr	synonymous	Exon 11 of 13	ENSP00000454786.2	H3BNC9
	RPS17	ENST00000560229.6	TSL:1	n.481T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40180 AN: 151992 Hom.: 5747 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.310 AC: 452667 AN: 1461016 Hom.: 72396 Cov.: 34 AF XY: 0.315 AC XY: 228914 AN XY: 726838

African (AFR) AF: 0.158 AC: 5284 AN: 33466

American (AMR) AF: 0.163 AC: 7284 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 8143 AN: 26132

East Asian (EAS) AF: 0.279 AC: 11075 AN: 39696

South Asian (SAS) AF: 0.421 AC: 36258 AN: 86224

European-Finnish (FIN) AF: 0.377 AC: 20130 AN: 53416

Middle Eastern (MID) AF: 0.336 AC: 1935 AN: 5756

European-Non Finnish (NFE) AF: 0.309 AC: 343756 AN: 1111262

Other (OTH) AF: 0.312 AC: 18802 AN: 60348

GnomAD4 genome AF: 0.264 AC: 40172 AN: 152110 Hom.: 5746 Cov.: 32 AF XY: 0.267 AC XY: 19847 AN XY: 74364

African (AFR) AF: 0.165 AC: 6852 AN: 41490

American (AMR) AF: 0.204 AC: 3123 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1028 AN: 3466

East Asian (EAS) AF: 0.236 AC: 1223 AN: 5174

South Asian (SAS) AF: 0.416 AC: 2009 AN: 4824

European-Finnish (FIN) AF: 0.369 AC: 3902 AN: 10566

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20987 AN: 67988

Other (OTH) AF: 0.277 AC: 583 AN: 2106

Alfa AF: 0.264 Hom.: 525

Bravo AF: 0.243

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	not specified (2)
-	-	1	Diamond-Blackfan anemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.3
DANN	Benign	0.68
PhyloP100		3.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=79/21	polymorphism

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: rs6991; hg19: chr15-83207733;