rs778991657

Variant names:

• chr1-74736560-G-A
• rs778991657
• NM_138467.3:c.193G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-74736560-G-A
• chr1-74736560-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138467.3(TYW3):​c.193G>A​(p.Val65Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. V65F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TYW3 NM_138467.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.832

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]

ACMG classification

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=0.067701966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYW3	NM_138467.3	c.193G>A	p.Val65Ile	missense_variant	Exon 2 of 6	ENST00000370867.8	NP_612476.1
TYW3	NM_001162916.2	c.193G>A	p.Val65Ile	missense_variant	Exon 2 of 5		NP_001156388.1
TYW3	XM_006710347.3	c.193G>A	p.Val65Ile	missense_variant	Exon 2 of 7		XP_006710410.1
TYW3	NR_027962.2	n.399G>A		non_coding_transcript_exon_variant	Exon 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYW3	ENST00000370867.8	c.193G>A	p.Val65Ile	missense_variant	Exon 2 of 6	1	NM_138467.3	ENSP00000359904.3
TYW3	ENST00000457880.6	c.193G>A	p.Val65Ile	missense_variant	Exon 2 of 5	2		ENSP00000407025.2
TYW3	ENST00000479111	c.-168G>A		5_prime_UTR_variant	Exon 3 of 7	3		ENSP00000477469.1
TYW3	ENST00000483990	c.-168G>A		5_prime_UTR_variant	Exon 1 of 4	3		ENSP00000476365.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448692 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 720158

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000229

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.80
DEOGEN2	Benign	0.0052	.;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.068	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	L;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.020
Sift	Benign	0.51	T;T
Sift4G	Benign	0.55	T;T
Polyphen		0.0040	.;B
Vest4		0.091
MutPred		0.51		Loss of ubiquitination at K67 (P = 0.0997);Loss of ubiquitination at K67 (P = 0.0997);
MVP		0.23
MPC		0.079
ClinPred		0.16	T
GERP RS		1.3
Varity_R		0.017
gMVP		0.12

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

Other links and lift over

dbSNP: rs778991657; hg19: chr1-75202244;