rs6966142

Variant names:

• chr7-67151617-C-G
• rs6966142
• NM_018264.4:c.1699-31509C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-67151617-C-G
• chr7-67151617-C-T

Variant summary

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

The NM_018264.4(TYW1):​c.1699-31509C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,930 control chromosomes in the GnomAD database, including 5,587 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 0.26 (5587 hom., cov: 32)
• Consequence: TYW1 NM_018264.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 4 publications found

Genes affected

TYW1 (HGNC:25598): (tRNA-yW synthesizing protein 1 homolog) Wybutosine (yW) is a hypermodified guanosine found in phenylalanine tRNA adjacent to the anticodon that stabilizes codon-anticodon interactions in the ribosome. In yeast, the homolog of this gene is essential for the synthesis of wybutosine. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

LOC124901666 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018264.4. 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
	TYW1	NM_018264.4	MANE Select	c.1699-31509C>G		intron	N/A	NP_060734.2
	TYW1	NR_134540.2		n.1792-31509C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYW1	ENST00000359626.10	TSL:1 MANE Select	c.1699-31509C>G		intron	N/A	ENSP00000352645.5
	TYW1	ENST00000361660.8	TSL:1	n.*491-31509C>G		intron	N/A	ENSP00000354795.4
	TYW1	ENST00000495971.1	TSL:2	n.691-31509C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39398 AN: 151812 Hom.: 5582 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0643

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.259 AC: 39424 AN: 151930 Hom.: 5587 Cov.: 32 AF XY: 0.254 AC XY: 18884 AN XY: 74248

African (AFR) AF: 0.377 AC: 15597 AN: 41406

American (AMR) AF: 0.210 AC: 3209 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 884 AN: 3470

East Asian (EAS) AF: 0.0641 AC: 331 AN: 5166

South Asian (SAS) AF: 0.286 AC: 1374 AN: 4812

European-Finnish (FIN) AF: 0.143 AC: 1509 AN: 10542

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.230 AC: 15615 AN: 67964

Other (OTH) AF: 0.240 AC: 507 AN: 2110

Alfa AF: 0.147 Hom.: 254

Bravo AF: 0.265

Asia WGS AF: 0.201 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.63
PhyloP100		-0.085
Mutation Taster		=100/0	polymorphism (auto)

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: rs6966142; hg19: chr7-66616604; COSMIC: COSV107450205;