chr8-63191534-A-G

Variant names:

• chr8-63191534-A-G
• rs4739066
• NM_152758.6:c.1734+3789A>G

Variant summary

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

The NM_152758.6(YTHDF3):​c.1734+3789A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,152 control chromosomes in the GnomAD database, including 1,463 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 0.12 (1463 hom., cov: 32)
• Consequence: YTHDF3 NM_152758.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.706
• Publications: 10 publications found

Genes affected

YTHDF3 (HGNC:26465): (YTH N6-methyladenosine RNA binding protein F3) This gene encodes a member of the YTH (YT521-B homology) domain protein family. The YTH domain is common in eukaryotes, is often found in the middle of the protein sequence, and may function in binding to RNA. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YTHDF3	NM_152758.6	c.1734+3789A>G		intron_variant	Intron 4 of 4	ENST00000539294.6	NP_689971.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YTHDF3	ENST00000539294.6	c.1734+3789A>G		intron_variant	Intron 4 of 4	1	NM_152758.6	ENSP00000473496.2

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18420 AN: 152034 Hom.: 1460 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.0846

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.121 AC: 18437 AN: 152152 Hom.: 1463 Cov.: 32 AF XY: 0.123 AC XY: 9117 AN XY: 74398

African (AFR) AF: 0.191 AC: 7913 AN: 41468

American (AMR) AF: 0.147 AC: 2254 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3472

East Asian (EAS) AF: 0.353 AC: 1826 AN: 5170

South Asian (SAS) AF: 0.0487 AC: 235 AN: 4824

European-Finnish (FIN) AF: 0.0846 AC: 896 AN: 10590

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0665 AC: 4526 AN: 68018

Other (OTH) AF: 0.101 AC: 213 AN: 2114

Alfa AF: 0.0885 Hom.: 2399

Bravo AF: 0.132

Asia WGS AF: 0.168 AC: 582 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.8
DANN	Benign	0.78
PhyloP100		0.71
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: rs4739066; hg19: chr8-64104092;