Genetic Variant TYW3:p.Lys207Asn (chr1-74763954-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138467.3(TYW3):c.621G>T(p.Lys207Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,216 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TYW3
NM_138467.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

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 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=0.10221404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYW3	NM_138467.3 link	c.621G>T	p.Lys207Asn	missense_variant	Exon 6 of 6	ENST00000370867.8	NP_612476.1	Q6IPR3-1
TYW3	NM_001162916.2 link	c.522G>T	p.Lys174Asn	missense_variant	Exon 5 of 5		NP_001156388.1	Q6IPR3-2Q96GE7
TYW3	XM_006710347.3 link	c.621G>T	p.Lys207Asn	missense_variant	Exon 6 of 7		XP_006710410.1	Q6IPR3-1
TYW3	NR_027962.2 link	n.827G>T		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYW3	ENST00000370867.8 link	c.621G>T	p.Lys207Asn	missense_variant	Exon 6 of 6	1	NM_138467.3	ENSP00000359904.3		Q6IPR3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000808

AC:

AN:

247622

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133702

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000684

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457216

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724606

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:

0.0000236

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.621G>T (p.K207N) alteration is located in exon 6 (coding exon 6) of the TYW3 gene. This alteration results from a G to T substitution at nucleotide position 621, causing the lysine (K) at amino acid position 207 to be replaced by an asparagine (N). 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

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0026

.;T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

.;M;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.2

N;N;.

REVEL

Benign

0.075

Sift

Benign

0.061

T;T;.

Sift4G

Benign

0.18

T;T;T

Polyphen

0.50

.;P;.

Vest4

0.072

MutPred

0.17

.;Loss of ubiquitination at K207 (P = 0.0047);.;

MVP

0.25

MPC

0.11

ClinPred

0.10

GERP RS

2.2

Varity_R

0.061

gMVP

0.16

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