rs535173722

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145440.3(TYW1B):​c.472G>T​(p.Val158Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V158M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

TYW1B
NM_001145440.3 missense

Scores

6
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.86
Variant links:
Genes affected
TYW1B (HGNC:33908): (tRNA-yW synthesizing protein 1 homolog B) Wybutosine is a hypermodified guanosine found in phenylalanine tRNA. Wybutosine functions to stabilize codon-anticodon interactions during ribosome decoding and therefore supports the maintenance of the reading frame. In yeast, the homolog of this gene is essential for the synthesis of wybutosine. The human genome contains two closely related genes that putatively function in wybutosine synthesis. The open reading frame of this locus is disrupted in some individuals. Thus, this locus appears to be an evolving pseudogene, but may still be functional in some members of the population. [provided by RefSeq, Apr 2014]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TYW1BNM_001145440.3 linkc.472G>T p.Val158Leu missense_variant Exon 5 of 14 ENST00000620995.5 NP_001138912.2 Q6NUM6-1
TYW1BNM_001412179.1 linkc.472G>T p.Val158Leu missense_variant Exon 5 of 12 NP_001399108.1
TYW1BNM_001412180.1 linkc.472G>T p.Val158Leu missense_variant Exon 5 of 11 NP_001399109.1
TYW1BNM_001412181.1 linkc.472G>T p.Val158Leu missense_variant Exon 5 of 5 NP_001399110.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TYW1BENST00000620995.5 linkc.472G>T p.Val158Leu missense_variant Exon 5 of 14 1 NM_001145440.3 ENSP00000482502.1 Q6NUM6-1
TYW1BENST00000612372.4 linkc.238-4795G>T intron_variant Intron 3 of 11 1 ENSP00000480534.1 A0A087WWV6
TYW1BENST00000610600.1 linkc.277G>T p.Val93Leu missense_variant Exon 4 of 8 2 ENSP00000484480.1 A0A087X1V1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461740
Hom.:
0
Cov.:
87
AF XY:
0.00000963
AC XY:
7
AN XY:
727148
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Uncertain
0.022
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
21
DANN
Benign
0.73
DEOGEN2
Benign
0.024
T;.
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.0014
T
MetaRNN
Uncertain
0.49
T;T
PrimateAI
Uncertain
0.75
T
Sift4G
Uncertain
0.0030
D;D
Polyphen
0.043
B;.
Vest4
0.18
MVP
0.35
GERP RS
2.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.080
gMVP
0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-72277910; API