chr8-63191534-A-G

Position:

• chr8-63191534-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
YTHDF3	NM_152758.6	c.1734+3789A>G		intron_variant		ENST00000539294.6	NP_689971.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YTHDF3	ENST00000539294.6	c.1734+3789A>G		intron_variant		1	NM_152758.6	ENSP00000473496	P4

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

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.0487

Gnomad4 FIN AF: 0.0846

Gnomad4 NFE AF: 0.0665

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0788 Hom.: 1305

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4739066; hg19: chr8-64104092;