Variant 1-74763925-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138467.3(TYW3):c.592A>G(p.Arg198Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000804 in 1,604,376 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 1 hom. )

Consequence

TYW3
NM_138467.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90

Variant links:

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]

TYW3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.013949782).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TYW3	NM_138467.3 linkuse as main transcript	c.592A>G	p.Arg198Gly	missense_variant	6/6	ENST00000370867.8	NP_612476.1
TYW3	NM_001162916.2 linkuse as main transcript	c.493A>G	p.Arg165Gly	missense_variant	5/5		NP_001156388.1
TYW3	XM_006710347.3 linkuse as main transcript	c.592A>G	p.Arg198Gly	missense_variant	6/7		XP_006710410.1
TYW3	NR_027962.2 linkuse as main transcript	n.798A>G		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYW3	ENST00000370867.8 linkuse as main transcript	c.592A>G	p.Arg198Gly	missense_variant	6/6	1	NM_138467.3	ENSP00000359904	P1	Q6IPR3-1

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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

GnomAD3 exomes

AF:

0.000128

AC:

AN:

243104

Hom.:

AF XY:

0.000129

AC XY:

AN XY:

131416

show subpopulations

Gnomad AFR exome

AF:

0.00189

Gnomad AMR exome

AF:

0.0000303

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000420

AC:

AN:

1452230

Hom.:

Cov.:

AF XY:

0.0000402

AC XY:

AN XY:

722028

show subpopulations

Gnomad4 AFR exome

AF:

0.00157

Gnomad4 AMR exome

AF:

0.0000234

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000239

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.000447

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00162

Gnomad4 AMR

AF:

0.0000655

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

Alfa

AF:

0.000112

Hom.:

Bravo

AF:

0.000555

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000124

AC:

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

Feb 10, 2022

The c.592A>G (p.R198G) alteration is located in exon 6 (coding exon 6) of the TYW3 gene. This alteration results from a A to G substitution at nucleotide position 592, causing the arginine (R) at amino acid position 198 to be replaced by a glycine (G). 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

0.080

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0090

.;T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

.;M;.

MutationTaster

Benign

0.87

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.6

D;N;.

REVEL

Benign

0.056

Sift

Benign

0.062

T;T;.

Sift4G

Benign

0.38

T;T;T

Polyphen

0.34

.;B;.

Vest4

0.19

MVP

0.22

MPC

0.13

ClinPred

0.040

GERP RS

2.9

Varity_R

0.080

gMVP

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over