7-72807315-CAC-GAG

Variant names:

• chr7-72807315-CAC-GAG
• NM_001145440.3:c.472_474delGTGinsCTC
• TYW1B p.Val158Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001145440.3(TYW1B):​c.472_474delGTGinsCTC​(p.Val158Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in 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)
• Consequence: TYW1B NM_001145440.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.86
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145440.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYW1B	NM_001145440.3	MANE Select	c.472_474delGTGinsCTC	p.Val158Leu	missense	N/A	NP_001138912.2	Q6NUM6-1
	TYW1B	NM_001412179.1		c.472_474delGTGinsCTC	p.Val158Leu	missense	N/A	NP_001399108.1
	TYW1B	NM_001412180.1		c.472_474delGTGinsCTC	p.Val158Leu	missense	N/A	NP_001399109.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYW1B	ENST00000620995.5	TSL:1 MANE Select	c.472_474delGTGinsCTC	p.Val158Leu	missense	N/A	ENSP00000482502.1	Q6NUM6-1
	TYW1B	ENST00000612372.4	TSL:1	c.238-4795_238-4793delGTGinsCTC		intron	N/A	ENSP00000480534.1	A0A087WWV6
	TYW1B	ENST00000902318.1		c.472_474delGTGinsCTC	p.Val158Leu	missense	N/A	ENSP00000572377.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-72277908;