NM_018264.4:c.1978-3511T>C

Variant names:

• chr7-67234797-T-C
• rs1465306
• NM_018264.4:c.1978-3511T>C

Variant summary

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

The NM_018264.4(TYW1):​c.1978-3511T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,900 control chromosomes in the GnomAD database, including 12,177 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 0.39 (12177 hom., cov: 31)
• Consequence: TYW1 NM_018264.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 6 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]

ENSG00000291154 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYW1	NM_018264.4	c.1978-3511T>C		intron_variant	Intron 15 of 15	ENST00000359626.10	NP_060734.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYW1	ENST00000359626.10	c.1978-3511T>C		intron_variant	Intron 15 of 15	1	NM_018264.4	ENSP00000352645.5

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58568 AN: 151782 Hom.: 12147 Cov.: 31

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.386 AC: 58640 AN: 151900 Hom.: 12177 Cov.: 31 AF XY: 0.388 AC XY: 28831 AN XY: 74254

African (AFR) AF: 0.540 AC: 22372 AN: 41418

American (AMR) AF: 0.443 AC: 6760 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1079 AN: 3470

East Asian (EAS) AF: 0.322 AC: 1657 AN: 5150

South Asian (SAS) AF: 0.368 AC: 1767 AN: 4804

European-Finnish (FIN) AF: 0.309 AC: 3255 AN: 10542

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20444 AN: 67962

Other (OTH) AF: 0.372 AC: 784 AN: 2108

Alfa AF: 0.361 Hom.: 2016

Bravo AF: 0.401

Asia WGS AF: 0.384 AC: 1337 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.92
DANN	Benign	0.63
PhyloP100		-1.2
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: rs1465306; hg19: chr7-66699784;