rs16930253

Positions:

• chr8-63201708-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152758.6(YTHDF3):​c.1735-7975G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 152,184 control chromosomes in the GnomAD database, including 841 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 0.099 (841 hom., cov: 32)
• Consequence: YTHDF3 NM_152758.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YTHDF3	NM_152758.6	c.1735-7975G>T		intron_variant		ENST00000539294.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YTHDF3	ENST00000539294.6	c.1735-7975G>T		intron_variant		1	NM_152758.6	P4

Frequencies

GnomAD3 genomes AF: 0.0985 AC: 14985 AN: 152066 Hom.: 839 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0994

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.0808

Gnomad OTH AF: 0.0999

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

GnomAD4 genome AF: 0.0986 AC: 15005 AN: 152184 Hom.: 841 Cov.: 32 AF XY: 0.100 AC XY: 7465 AN XY: 74416

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0992

Gnomad4 ASJ AF: 0.0755

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.0808

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0868 Hom.: 117

Bravo AF: 0.0955

Asia WGS AF: 0.174 AC: 604 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.56

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: rs16930253; hg19: chr8-64114266;