chr7-72807317-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001145440.3(TYW1B):​c.472G>A​(p.Val158Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000335 in 1,614,014 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 2 hom. )

Consequence

TYW1B
NM_001145440.3 missense

Scores

1
3
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.19691214).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TYW1BNM_001145440.3 linkc.472G>A p.Val158Met missense_variant Exon 5 of 14 ENST00000620995.5 NP_001138912.2 Q6NUM6-1
TYW1BNM_001412179.1 linkc.472G>A p.Val158Met missense_variant Exon 5 of 12 NP_001399108.1
TYW1BNM_001412180.1 linkc.472G>A p.Val158Met missense_variant Exon 5 of 11 NP_001399109.1
TYW1BNM_001412181.1 linkc.472G>A p.Val158Met 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>A p.Val158Met missense_variant Exon 5 of 14 1 NM_001145440.3 ENSP00000482502.1 Q6NUM6-1
TYW1BENST00000612372.4 linkc.238-4795G>A intron_variant Intron 3 of 11 1 ENSP00000480534.1 A0A087WWV6
TYW1BENST00000610600.1 linkc.277G>A p.Val93Met missense_variant Exon 4 of 8 2 ENSP00000484480.1 A0A087X1V1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000756
AC:
19
AN:
251292
Hom.:
1
AF XY:
0.0000589
AC XY:
8
AN XY:
135810
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000457
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000322
AC:
47
AN:
1461740
Hom.:
2
Cov.:
87
AF XY:
0.0000399
AC XY:
29
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:
0.0000252
Gnomad4 SAS exome
AF:
0.000313
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152274
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.0000963
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000741
AC:
9

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 12, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.472G>A (p.V158M) alteration is located in exon 5 (coding exon 5) of the TYW1B gene. This alteration results from a G to A substitution at nucleotide position 472, causing the valine (V) at amino acid position 158 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.20
CADD
Uncertain
24
DANN
Benign
0.76
DEOGEN2
Benign
0.014
T;.
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Benign
0.0013
T
MetaRNN
Benign
0.20
T;T
PrimateAI
Uncertain
0.75
T
Sift4G
Pathogenic
0.0010
D;D
Polyphen
0.89
P;.
Vest4
0.21
MVP
0.35
GERP RS
2.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.063
gMVP
0.72

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: rs535173722; hg19: chr7-72277910; COSMIC: COSV101444352; API