15-82536888-C-T

Position:

• chr15-82536888-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001021.6(RPS17):​c.328-7G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,613,936 control chromosomes in the GnomAD database, including 6 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 0.0020 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (4 hom.)
• Consequence: RPS17 NM_001021.6 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00005533
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.739

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-82536888-C-T is Benign according to our data. Variant chr15-82536888-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 506484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 312 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS17	NM_001021.6	c.328-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000647841.1
RPS17	NR_111943.2	n.650-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant
RPS17	NR_111944.3	n.478-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS17	ENST00000647841.1	c.328-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001021.6	P1

Frequencies

GnomAD3 genomes AF: 0.00205 AC: 312 AN: 152162 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00538

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00328

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.00235 AC: 3428 AN: 1461656 Hom.: 4 Cov.: 31 AF XY: 0.00237 AC XY: 1720 AN XY: 727138

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00348

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000452

Gnomad4 FIN exome AF: 0.00603

Gnomad4 NFE exome AF: 0.00256

Gnomad4 OTH exome AF: 0.00182

GnomAD4 genome AF: 0.00205 AC: 312 AN: 152280 Hom.: 2 Cov.: 32 AF XY: 0.00212 AC XY: 158 AN XY: 74458

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00538

Gnomad4 NFE AF: 0.00328

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00199 Hom.: 1

Bravo AF: 0.00143

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 16, 2021

- -

Diamond-Blackfan anemia 4 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000055
dbscSNV1_RF	Benign	0.0060
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: rs975130647; hg19: chr15-83205639;