1-74752328-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_138467.3(TYW3):c.463A>G(p.Ser155Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,612,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
TYW3
NM_138467.3 missense
NM_138467.3 missense
Scores
1
3
13
Clinical Significance
Conservation
PhyloP100: 6.28
Genes affected
TYW3 (HGNC:24757): (tRNA-yW synthesizing protein 3 homolog) Wybutosine (yW) is a hypermodified guanosine at the 3-prime position adjacent to the anticodon of phenylalanine tRNA that stabilizes codon-anticodon interactions during decoding on the ribosome. TYW3 is the human homolog of a yeast gene essential for yW synthesis (Noma and Suzuki, 2006).[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.086616814).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYW3 | NM_138467.3 | c.463A>G | p.Ser155Gly | missense_variant | 5/6 | ENST00000370867.8 | |
TYW3 | NM_001162916.2 | c.364A>G | p.Ser122Gly | missense_variant | 4/5 | ||
TYW3 | XM_006710347.3 | c.463A>G | p.Ser155Gly | missense_variant | 5/7 | ||
TYW3 | NR_027962.2 | n.669A>G | non_coding_transcript_exon_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYW3 | ENST00000370867.8 | c.463A>G | p.Ser155Gly | missense_variant | 5/6 | 1 | NM_138467.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152198Hom.: 0 Cov.: 33
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?
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251010Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135636
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GnomAD4 genome ? AF: 0.0000986 AC: 15AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74350
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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 | Jan 03, 2022 | The c.463A>G (p.S155G) alteration is located in exon 5 (coding exon 5) of the TYW3 gene. This alteration results from a A to G substitution at nucleotide position 463, causing the serine (S) at amino acid position 155 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;.;.
REVEL
Benign
Sift
Benign
T;T;.;.
Sift4G
Benign
T;T;D;D
Polyphen
0.14
.;B;.;.
Vest4
MVP
MPC
0.26
ClinPred
T
GERP RS
Varity_R
gMVP
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