rs6460033

Variant names:

• chr7-72798898-A-C
• rs6460033
• NM_001145440.3:c.846+3502T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-72798898-A-C
• chr7-72798898-A-G
• chr7-72798898-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145440.3(TYW1B):​c.846+3502T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 152,064 control chromosomes in the GnomAD database, including 36,789 homozygotes. 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: 𝑓 0.69 (36789 hom., cov: 33)
• Consequence: TYW1B NM_001145440.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.964
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYW1B	NM_001145440.3	c.846+3502T>G		intron_variant	Intron 6 of 13	ENST00000620995.5	NP_001138912.2
TYW1B	NM_001412179.1	c.846+3502T>G		intron_variant	Intron 6 of 11		NP_001399108.1
TYW1B	NM_001412180.1	c.846+3502T>G		intron_variant	Intron 6 of 10		NP_001399109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYW1B	ENST00000620995.5	c.846+3502T>G		intron_variant	Intron 6 of 13	1	NM_001145440.3	ENSP00000482502.1
TYW1B	ENST00000612372.4	c.360+3502T>G		intron_variant	Intron 4 of 11	1		ENSP00000480534.1
TYW1B	ENST00000610600.1	c.651+3502T>G		intron_variant	Intron 5 of 7	2		ENSP00000484480.1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104400 AN: 151946 Hom.: 36784 Cov.: 33

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.687 AC: 104434 AN: 152064 Hom.: 36789 Cov.: 33 AF XY: 0.686 AC XY: 50988 AN XY: 74354

African (AFR) AF: 0.564 AC: 23361 AN: 41444

American (AMR) AF: 0.665 AC: 10146 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2511 AN: 3472

East Asian (EAS) AF: 0.446 AC: 2305 AN: 5168

South Asian (SAS) AF: 0.666 AC: 3208 AN: 4820

European-Finnish (FIN) AF: 0.790 AC: 8364 AN: 10588

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.767 AC: 52150 AN: 68006

Other (OTH) AF: 0.689 AC: 1452 AN: 2108

Alfa AF: 0.743 Hom.: 17487

Bravo AF: 0.673

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	7.1
PhyloP100		0.96

Splicing

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

Other links and lift over

dbSNP: rs6460033; hg19: chr7-72263918;