7-72664689-C-T

Variant names:

• chr7-72664689-C-T
• rs13238203
• NM_001145440.3:c.1506+29998G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001145440.3(TYW1B):​c.1506+29998G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 152,048 control chromosomes in the GnomAD database, including 42 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 0.019 (42 hom., cov: 32)
• Consequence: TYW1B NM_001145440.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 53 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=-1.01).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0186 (2835/152048) while in subpopulation SAS AF = 0.0374 (180/4814). AF 95% confidence interval is 0.0329. There are 42 homozygotes in GnomAd4. There are 1414 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYW1B	NM_001145440.3	c.1506+29998G>A		intron_variant	Intron 11 of 13	ENST00000620995.5	NP_001138912.2
TYW1B	NM_001412179.1	c.1278+29998G>A		intron_variant	Intron 9 of 11		NP_001399108.1
TYW1B	NM_001412180.1	c.1278+29998G>A		intron_variant	Intron 9 of 10		NP_001399109.1
TYW1B	NM_001412182.1	c.384+29998G>A		intron_variant	Intron 4 of 6		NP_001399111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYW1B	ENST00000620995.5	c.1506+29998G>A		intron_variant	Intron 11 of 13	1	NM_001145440.3	ENSP00000482502.1
TYW1B	ENST00000612372.4	c.1020+29998G>A		intron_variant	Intron 9 of 11	1		ENSP00000480534.1

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2833 AN: 151930 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.00472

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0374

Gnomad FIN AF: 0.0177

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0292

Gnomad OTH AF: 0.0129

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

GnomAD4 genome AF: 0.0186 AC: 2835 AN: 152048 Hom.: 42 Cov.: 32 AF XY: 0.0190 AC XY: 1414 AN XY: 74320

African (AFR) AF: 0.00475 AC: 197 AN: 41470

American (AMR) AF: 0.0131 AC: 200 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 47 AN: 3460

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5172

South Asian (SAS) AF: 0.0374 AC: 180 AN: 4814

European-Finnish (FIN) AF: 0.0177 AC: 187 AN: 10560

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0292 AC: 1985 AN: 67992

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.0133 Hom.: 3

Bravo AF: 0.0160

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.44
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

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: rs13238203; hg19: chr7-72129667;