19-39433567-T-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001020.6(RPS16):āc.250A>Cā(p.Ile84Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000372 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000034 ( 0 hom. )
Consequence
RPS16
NM_001020.6 missense, splice_region
NM_001020.6 missense, splice_region
Scores
2
8
5
Clinical Significance
Conservation
PhyloP100: 5.70
Genes affected
RPS16 (HGNC:10396): (ribosomal protein S16) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 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 S9P family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]
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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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPS16 | NM_001020.6 | c.250A>C | p.Ile84Leu | missense_variant, splice_region_variant | 4/5 | ENST00000251453.8 | |
RPS16 | NM_001321111.2 | c.199A>C | p.Ile67Leu | missense_variant, splice_region_variant | 4/5 | ||
RPS16 | NM_001363860.2 | c.345A>C | p.Leu115= | synonymous_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPS16 | ENST00000251453.8 | c.250A>C | p.Ile84Leu | missense_variant, splice_region_variant | 4/5 | 1 | NM_001020.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251492Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135918
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461890Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727248
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74360
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 29, 2022 | The c.250A>C (p.I84L) alteration is located in exon 4 (coding exon 4) of the RPS16 gene. This alteration results from a A to C substitution at nucleotide position 250, causing the isoleucine (I) at amino acid position 84 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
Sift4G
Benign
T;D;T;T;T
Polyphen
0.0010
.;B;.;.;.
Vest4
MVP
MPC
1.5
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at