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15-82538321-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001021.6(RPS17):c.312A>G(p.Glu104=) 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

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0510
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPS17NM_001021.6 linkuse as main transcriptc.312A>G p.Glu104= synonymous_variant 4/5 ENST00000647841.1
RPS17NR_111943.2 linkuse as main transcriptn.634A>G non_coding_transcript_exon_variant 3/4
RPS17NR_111944.3 linkuse as main transcriptn.341A>G non_coding_transcript_exon_variant 4/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPS17ENST00000647841.1 linkuse as main transcriptc.312A>G p.Glu104= synonymous_variant 4/5 NM_001021.6 P1

Frequencies

GnomAD3 genomes
AF:
0.0221
AC:
3363
AN:
152172
Hom.:
123
Cov.:
32
show subpopulations
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0783
Gnomad4 AMR exome
AF:
0.00445
Gnomad4 ASJ exome
AF:
0.000344
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000137
Gnomad4 OTH exome
AF:
0.00469
GnomAD4 genome
AF:
0.0221
AC:
3361
AN:
152290
Hom.:
123
Cov.:
32
AF XY:
0.0216
AC XY:
1605
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.0759
Gnomad4 AMR
AF:
0.0101
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.0137
Alfa
AF:
0.0184
Hom.:
5
Bravo
AF:
0.0260

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Diamond-Blackfan anemia 4 Benign:1
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsOct 18, 2021- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxOct 15, 2018This variant is associated with the following publications: (PMID: 20054847) -
Diamond-Blackfan anemia Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsAug 20, 2014This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
6.9
Dann
Benign
0.91
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1049218128; hg19: chr15-83207072; API