7-72804517-C-A

Variant names:

• chr7-72804517-C-A
• rs6945435
• NM_001145440.3:c.724-1995G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145440.3(TYW1B):​c.724-1995G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TYW1B NM_001145440.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (Cadd=1.177).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYW1B	NM_001145440.3	MANE Select	c.724-1995G>T		intron	N/A	NP_001138912.2
	TYW1B	NM_001412179.1		c.724-1995G>T		intron	N/A	NP_001399108.1
	TYW1B	NM_001412180.1		c.724-1995G>T		intron	N/A	NP_001399109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYW1B	ENST00000620995.5	TSL:1 MANE Select	c.724-1995G>T		intron	N/A	ENSP00000482502.1
	TYW1B	ENST00000612372.4	TSL:1	c.238-1995G>T		intron	N/A	ENSP00000480534.1
	TYW1B	ENST00000610600.1	TSL:2	c.529-1995G>T		intron	N/A	ENSP00000484480.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	1.2
PhyloP100		-0.97

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

Other links and lift over

dbSNP: rs6945435;