rs4717344

Variant names:

• chr7-67021557-C-T
• rs4717344
• NM_018264.4:c.862-3343C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_018264.4(TYW1):​c.862-3343C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 151,680 control chromosomes in the GnomAD database, including 101 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 0.11 (101 hom., cov: 41)
• Consequence: TYW1 NM_018264.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538
• 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS2: High Homozygotes in GnomAd4 at 101 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYW1	NM_018264.4	c.862-3343C>T		intron_variant	Intron 6 of 15	ENST00000359626.10	NP_060734.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYW1	ENST00000359626.10	c.862-3343C>T		intron_variant	Intron 6 of 15	1	NM_018264.4	ENSP00000352645.5
TYW1	ENST00000361660.8	n.862-3343C>T		intron_variant	Intron 6 of 14	1		ENSP00000354795.4

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17184 AN: 151558 Hom.: 101 Cov.: 41

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0572

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.144

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.113 AC: 17195 AN: 151680 Hom.: 101 Cov.: 41 AF XY: 0.115 AC XY: 8551 AN XY: 74172

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0642 AC: 2664 AN: 41474

American (AMR) AF: 0.141 AC: 2135 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 462 AN: 3456

East Asian (EAS) AF: 0.0571 AC: 296 AN: 5184

South Asian (SAS) AF: 0.129 AC: 624 AN: 4820

European-Finnish (FIN) AF: 0.148 AC: 1563 AN: 10540

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8887 AN: 67708

Other (OTH) AF: 0.146 AC: 306 AN: 2102

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.119 Hom.: 591

Asia WGS AF: 0.102 AC: 354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.83
PhyloP100		-0.54
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: rs4717344; hg19: chr7-66486544;