15-82538981-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001021.6(RPS17):​c.160G>A​(p.Val54Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,790 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

RPS17
NM_001021.6 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPS17NM_001021.6 linkc.160G>A p.Val54Ile missense_variant Exon 3 of 5 ENST00000647841.1 NP_001012.1 P08708
RPS17NR_111943.2 linkn.482G>A non_coding_transcript_exon_variant Exon 2 of 4
RPS17NR_111944.3 linkn.189G>A non_coding_transcript_exon_variant Exon 3 of 6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPS17ENST00000647841.1 linkc.160G>A p.Val54Ile missense_variant Exon 3 of 5 NM_001021.6 ENSP00000498019.1 P08708
ENSG00000260836ENST00000562833.2 linkc.1507G>A p.Val503Ile missense_variant Exon 11 of 13 3 ENSP00000454786.2 H3BNC9

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152158
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461632
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
727132
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152158
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Diamond-Blackfan anemia 4 Uncertain:1
Feb 12, 2024
Fulgent Genetics, Fulgent Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Uncertain
0.063
T
BayesDel_noAF
Benign
-0.15
CADD
Uncertain
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.10
T;T;T;.
Eigen
Uncertain
0.25
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
.;D;D;D
M_CAP
Pathogenic
0.47
D
MetaRNN
Uncertain
0.66
D;D;D;D
MetaSVM
Uncertain
-0.086
T
MutationAssessor
Benign
1.8
L;L;.;.
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-0.80
.;N;N;.
REVEL
Uncertain
0.30
Sift
Benign
0.14
.;T;T;.
Sift4G
Benign
0.21
.;T;T;.
Vest4
0.37, 0.38
MutPred
0.54
Gain of methylation at K49 (P = 0.1132);Gain of methylation at K49 (P = 0.1132);Gain of methylation at K49 (P = 0.1132);.;
MVP
0.35
ClinPred
0.81
D
GERP RS
4.3
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.24
gMVP
0.50

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: rs1222131687; hg19: chr15-83207732; API